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Sample records for added metabolic activation

  1. Somatostatin Modulates Insulin-Degrading-Enzyme Metabolism: Implications for the Regulation of Microglia Activity in AD

    PubMed Central

    Tundo, Grazia; Ciaccio, Chiara; Sbardella, Diego; Boraso, Mariaserena; Viviani, Barbara; Coletta, Massimiliano; Marini, Stefano

    2012-01-01

    The deposition of β-amyloid (Aβ) into senile plaques and the impairment of somatostatin-mediated neurotransmission are key pathological events in the onset of Alzheimer's disease (AD). Insulin-degrading-enzyme (IDE) is one of the main extracellular protease targeting Aβ, and thus it represents an interesting pharmacological target for AD therapy. We show that the active form of somatostatin-14 regulates IDE activity by affecting its expression and secretion in microglia cells. A similar effect can also be observed when adding octreotide. Following a previous observation where somatostatin directly interacts with IDE, here we demonstrate that somatostatin regulates Aβ catabolism by modulating IDE proteolytic activity in IDE gene-silencing experiments. As a whole, these data indicate the relevant role played by somatostatin and, potentially, by analogue octreotide, in preventing Aβ accumulation by partially restoring IDE activity. PMID:22509294

  2. Metabolism Supports Macrophage Activation

    PubMed Central

    Langston, P. Kent; Shibata, Munehiko; Horng, Tiffany

    2017-01-01

    Macrophages are found in most tissues of the body, where they have tissue- and context-dependent roles in maintaining homeostasis as well as coordinating adaptive responses to various stresses. Their capacity for specialized functions is controlled by polarizing signals, which activate macrophages by upregulating transcriptional programs that encode distinct effector functions. An important conceptual advance in the field of macrophage biology, emerging from recent studies, is that macrophage activation is critically supported by metabolic shifts. Metabolic shifts fuel multiple aspects of macrophage activation, and preventing these shifts impairs appropriate activation. These findings raise the exciting possibility that macrophage functions in various contexts could be regulated by manipulating their metabolism. Here, we review the rapidly evolving field of macrophage metabolism, discussing how polarizing signals trigger metabolic shifts and how these shifts enable appropriate activation and sustain effector activities. We also discuss recent studies indicating that the mitochondria are central hubs in inflammatory macrophage activation. PMID:28197151

  3. Excitation function for deuteron induced nuclear reactions on natural ytterbium for production of high specific activity 177g Lu in no-carrier-added form for metabolic radiotherapy.

    PubMed

    Manenti, Simone; Groppi, Flavia; Gandini, Andrea; Gini, Luigi; Abbas, Kamel; Holzwarth, Uwe; Simonelli, Federica; Bonardi, Mauro

    2011-01-01

    Deuteron-induced nuclear reactions for generation of no-carrier-added Lu radionuclides were investigated using the stacked-foil activation technique on natural Yb targets at energies up to E(d)=18.18 MeV. Excitation functions of the reactions (nat)Yb(d,xn)(169,170,171,172,173,174g,174m,176m,177g)Lu and (nat)Yb(d,pxn)(169,175,177)Yb have been measured, among them three ((169)Lu, (174m)Lu and (176m)Lu) are reported for the first time. The upper limit of the contamination from the long-lived metastable level (177m)Lu was evaluated too. Thick-target yields for all investigated radionuclides are calculated.

  4. In silico strain optimization by adding reactions to metabolic models.

    PubMed

    Correia, Sara; Rocha, Miguel

    2012-07-24

    Nowadays, the concerns about the environment and the needs to increase the productivity at low costs, demand for the search of new ways to produce compounds with industrial interest. Based on the increasing knowledge of biological processes, through genome sequencing projects, and high-throughput experimental techniques as well as the available computational tools, the use of microorganisms has been considered as an approach to produce desirable compounds. However, this usually requires to manipulate these organisms by genetic engineering and/ or changing the enviromental conditions to make the production of these compounds possible. In many cases, it is necessary to enrich the genetic material of those microbes with hereologous pathways from other species and consequently adding the potential to produce novel compounds. This paper introduces a new plug-in for the OptFlux Metabolic Engineering platform, aimed at finding suitable sets of reactions to add to the genomes of selected microbes (wild type strain), as well as finding complementary sets of deletions, so that the mutant becomes able to overproduce compounds with industrial interest, while preserving their viability. The necessity of adding reactions to the metabolic model arises from existing gaps in the original model or motivated by the productions of new compounds by the organism. The optimization methods used are metaheuristics such as Evolutionary Algorithms and Simulated Annealing. The usefulness of this plug-in is demonstrated by a case study, regarding the production of vanillin by the bacterium E. coli.

  5. Effects of manganese deficiency and added cerium on nitrogen metabolism of maize.

    PubMed

    Gong, Xiaolan; Qu, Chunxiang; Liu, Chao; Hong, Mengmeng; Wang, Ling; Hong, Fashui

    2011-12-01

    Manganese is one of the essential microelements for plant growth, and cerium is a beneficial element for plant growth. However, whether manganese deficiency affects nitrogen metabolism of plants and cerium improves the nitrogen metabolism of plants by exposure to manganese-deficient media are still unclear. The main aim of the study was to determine the effects of manganese deficiency in nitrogen metabolism and the roles of cerium in the improvement of manganese-deficient effects in maize seedlings. Maize seedlings were cultivated in manganese present Meider's nutrient solution. They were subjected to manganese deficiency and to cerium chloride administered in the manganese-present and manganese-deficient media. Maize seedlings grown in the various media were measured for key enzyme activities involved in nitrogen metabolism, such as nitrate reductase, glutamate dehydrogenase, glutamine synthetase, and glutamic-oxaloace transaminase. We found that manganese deficiency restricted uptake and transport of NO(3)(-), inhibited activities of nitrogen-metabolism-related enzymes, such as nitrate reductase, glutamine synthetase, and glutamic-oxaloace transaminase, thus decreasing the synthesis of chlorophyll and soluble protein, and inhibited the growth of maize seedlings. Manganese deficiency promoted the activity of glutamate dehydrogenase and reduced the toxicity of excess ammonia to the plant, while added cerium relieved the damage to nitrogen metabolism caused by manganese deficiency in maize seedlings. However, cerium addition exerted positively to relieve the damage of nitrogen metabolism process in maize seedlings caused by exposure to manganese-deficient media.

  6. POSSIBLE CHROMOSPHERIC ACTIVITY CYCLES IN AD LEO

    SciTech Connect

    Buccino, Andrea P.; Petrucci, Romina; Mauas, Pablo J. D.; Jofré, Emiliano

    2014-01-20

    AD Leo (GJ 388) is an active dM3 flare star that has been extensively observed both in the quiescent and flaring states. Since this active star is near the fully convective boundary, studying its long-term chromospheric activity in detail could be an appreciable contribution to dynamo theory. Here, using the Lomb-Scargle periodogram, we analyze the Ca II K line-core fluxes derived from CASLEO spectra obtained between 2001 and 2013 and the V magnitude from the ASAS database between 2004 and 2010. From both of these totally independent time series, we obtain a possible activity cycle with a period of approximately seven years and a less significant shorter cycle of approximately two years. A tentative interpretation is that a dynamo operating near the surface could be generating the longer cycle, while a second dynamo operating in the deep convection zone could be responsible for the shorter one. Based on the long duration of our observing program at CASLEO and the fact that we observe different spectral features simultaneously, we also analyze the relation between simultaneous measurements of the Na I index (R{sub D}{sup ′}), Hα, and Ca II K fluxes at different activity levels of AD Leo, including flares.

  7. Metabolic cost of extravehicular activities

    NASA Technical Reports Server (NTRS)

    Waligora, J. M.; Horrigan, D. J., Jr.

    1974-01-01

    The data on metabolic rates during Skylab extravehicular activities are presented and compared with prior experience during Gemini and Apollo. Difficulties experienced with Gemini extravehicular activities are reviewed. The effect of a pressure suit on metabolic rate is discussed and the life support equipment capabilities of each life support system are reviewed. The methods used to measure metabolic rate, utilizing bioinstrumentation and operational data on the life support system, are described. Metabolic rates are correlated with different activities. Metabolic rates in Skylab were found to be within the capacities of the life support systems and to be similar to the metabolic rates experienced during Apollo lunar 1/6-g extravehicular activities. They were found to range from 100 kcal/h to 500 kcal/h, during both 1/6-g and zero-g extravehicular activities. The average metabolic rates measured during long extravehicular activities were remarkably consistent and appeared to be a function of crew pacing of activity rather than to the effort involved in individual tasks.

  8. Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD

    PubMed Central

    Colton, Carol A; Mott, Ryan T; Sharpe, Hayley; Xu, Qing; Van Nostrand, William E; Vitek, Michael P

    2006-01-01

    Background Microglia are associated with neuritic plaques in Alzheimer disease (AD) and serve as a primary component of the innate immune response in the brain. Neuritic plaques are fibrous deposits composed of the amyloid beta-peptide fragments (Abeta) of the amyloid precursor protein (APP). Numerous studies have shown that the immune cells in the vicinity of amyloid deposits in AD express mRNA and proteins for pro-inflammatory cytokines, leading to the hypothesis that microglia demonstrate classical (Th-1) immune activation in AD. Nonetheless, the complex role of microglial activation has yet to be fully explored since recent studies show that peripheral macrophages enter an "alternative" activation state. Methods To study alternative activation of microglia, we used quantitative RT-PCR to identify genes associated with alternative activation in microglia, including arginase I (AGI), mannose receptor (MRC1), found in inflammatory zone 1 (FIZZ1), and chitinase 3-like 3 (YM1). Results Our findings confirmed that treatment of microglia with anti-inflammatory cytokines such as IL-4 and IL-13 induces a gene profile typical of alternative activation similar to that previously observed in peripheral macrophages. We then used this gene expression profile to examine two mouse models of AD, the APPsw (Tg-2576) and Tg-SwDI, models for amyloid deposition and for cerebral amyloid angiopathy (CAA) respectively. AGI, MRC1 and YM1 mRNA levels were significantly increased in the Tg-2576 mouse brains compared to age-matched controls while TNFα and NOS2 mRNA levels, genes commonly associated with classical activation, increased or did not change, respectively. Only TNFα mRNA increased in the Tg-SwDI mouse brain. Alternative activation genes were also identified in brain samples from individuals with AD and were compared to age-matched control individuals. In AD brain, mRNAs for TNFα, AGI, MRC1 and the chitinase-3 like 1 and 2 genes (CHI3L1; CHI3L2) were significantly increased

  9. Pulmonary metabolism of foreign compounds: Its role in metabolic activation

    SciTech Connect

    Cohen, G.M. )

    1990-04-01

    The lung has the potential of metabolizing many foreign chemicals to a vast array of metabolites with different pharmacological and toxicological properties. Because many chemicals require metabolic activation in order to exert their toxicity, the cellular distribution of the drug-metabolizing enzymes in a heterogeneous tissue, such as the lung, and the balance of metabolic activation and deactivation pathways in any particular cell are key factors in determining the cellular specificity of many pulmonary toxins. Environmental factors such as air pollution, cigarette smoking, and diet markedly affect the pulmonary metabolism of some chemicals and, thereby, possibly affect their toxicity.

  10. Variations of 14C around AD 775 and AD 1795 - due to solar activity

    NASA Astrophysics Data System (ADS)

    Neuhäuser, R.; Neuhäuser, D. L.

    2015-12-01

    The motivation for our study is the disputed cause for the strong variation of 14C around AD 775. Our method is to compare the 14C variation around AD 775 with other periods of strong variability. Our results are: (a) We see three periods, where 14C varied over 200 yr in a special way showing a certain pattern of strong secular variation: after a Grand Minimum with strongly increasing 14C, there is a series of strong short-term drop(s), rise(s), and again drop(s) within 60 yr, ending up to 200 yr after the start of the Grand Minimum. These three periods include the strong rises around BC 671, AD 775, and AD 1795. (b) We show with several solar activity proxies (radioisotopes, sunspots, and aurorae) for the AD 770s and 1790s that such intense rapid 14C increases can be explained by strong rapid decreases in solar activity and, hence, wind, so that the decrease in solar modulation potential leads to an increase in radioisotope production. (c) The strong rises around AD 775 and 1795 are due to three effects, (i) very strong activity in the previous cycles (i.e. very low 14C level), (ii) the declining phase of a very strong Schwabe cycle, and (iii) a phase of very weak activity after the strong 14C rise - very short and/or weak cycle(s) like the suddenly starting Dalton minimum. (d) Furthermore, we can show that the strong change at AD 1795 happened after a pair of two packages of four Schwabe cycles with certain hemispheric leadership (each package consists of two Gnevyshev-Ohl pairs, respectively two Hale-Babcock pairs). We show with several additional arguments that the rise around AD 775 was not that special. We conclude that such large, short-term rises in 14C (around BC 671, AD 775, and 1795) do not need to be explained by highly unlikely solar super-flares nor other rare events, but by extra-solar cosmic rays modulated due to solar activity variations.

  11. Metabolic rate of carrying added mass: a function of walking speed, carried mass and mass location.

    PubMed

    Schertzer, Eliran; Riemer, Raziel

    2014-11-01

    The effort of carrying additional mass at different body locations is important in ergonomics and in designing wearable robotics. We investigate the metabolic rate of carrying a load as a function of its mass, its location on the body and the subject's walking speed. Novel metabolic rate prediction equations for walking while carrying loads at the ankle, knees and back were developed based on experiments where subjects walked on a treadmill at 4, 5 or 6km/h bearing different amounts of added mass (up to 2kg per leg and 22kg for back). Compared to previously reported equations, ours are 7-69% more accurate. Results also show that relative cost for carrying a mass at a distal versus a proximal location changes with speed and mass. Contrary to mass carried on the back, mass attached to the leg cannot be modeled as an increase in body mass.

  12. Viscosity dictates metabolic activity of Vibrio ruber

    PubMed Central

    Borić, Maja; Danevčič, Tjaša; Stopar, David

    2012-01-01

    Little is known about metabolic activity of bacteria, when viscosity of their environment changes. In this work, bacterial metabolic activity in media with viscosity ranging from 0.8 to 29.4 mPas was studied. Viscosities up to 2.4 mPas did not affect metabolic activity of Vibrio ruber. On the other hand, at 29.4 mPas respiration rate and total dehydrogenase activity increased 8 and 4-fold, respectively. The activity of glucose-6-phosphate dehydrogenase (GPD) increased up to 13-fold at higher viscosities. However, intensified metabolic activity did not result in faster growth rate. Increased viscosity delayed the onset as well as the duration of biosynthesis of prodigiosin. As an adaptation to viscous environment V. ruber increased metabolic flux through the pentose phosphate pathway and reduced synthesis of a secondary metabolite. In addition, V. ruber was able to modify the viscosity of its environment. PMID:22826705

  13. Solar activity around AD 775 from aurorae and radiocarbon

    NASA Astrophysics Data System (ADS)

    Neuhäuser, R.; Neuhäuser, D. L.

    2015-04-01

    A large variation in 14C around AD 775 has been considered to be caused by one or more solar super-flares within one year. We critically review all known aurora reports from Europe as well as the Near, Middle, and Far East from AD 731 to 825 and find 39 likely true aurorae plus four more potential aurorae and 24 other reports about halos, meteors, thunderstorms etc., which were previously misinterpreted as aurorae or misdated; we assign probabilities for all events according to five aurora criteria. We find very likely true aurorae in AD 743, 745, 762, 765, 772, 773, 793, 796, 807, and 817. There were two aurorae in the early 770s observed near Amida (now Diyarbak\\i r in Turkey near the Turkish-Syrian border), which were not only red, but also green-yellow - being at a relatively low geomagnetic latitude, they indicate a relatively strong solar storm. However, it cannot be argued that those aurorae (geomagnetic latitude 43 to 50°, considering five different reconstructions of the geomagnetic pole) could be connected to one or more solar super-flares causing the 14C increase around AD 775: There are several reports about low- to mid-latitude aurorae at 32 to 44° geomagnetic latitude in China and Iraq; some of them were likely observed (quasi-)simultaneously in two of three areas (Europe, Byzantium/Arabia, East Asia), one lasted several nights, and some indicate a particularly strong geomagnetic storm (red colour and dynamics), namely in AD 745, 762, 793, 807, and 817 - always without 14C peaks. We use 39 likely true aurorae as well as historic reports about sunspots together with the radiocarbon content from tree rings to reconstruct the solar activity: From AD {˜ 733} to {˜ 823}, we see at least nine Schwabe cycles; instead of one of those cycles, there could be two short, weak cycles - reflecting the rapid increase to a high 14C level since AD 775, which lies at the end of a strong cycle. In order to show the end of the dearth of naked-eye sunspots, we

  14. A Guide to Microsoft Active Directory (AD) Design

    SciTech Connect

    Dias, J

    2002-04-29

    The goal of this paper is to facilitate the design process for those DOE sites that are currently engaged in designing their Active Directory (AD) network. It is a roadmap to enable analysis of the complicated design tradeoffs associated with Active Directory Design. By providing discussion of Active Directory design elements which are permanent and costly to change once deployed, the hope is to minimize the risks of sponsoring failed designs, or joining existing infrastructures not suitable to programmatic needs. Specifically, most Active Directory structures will fall under one of three common designs: Single Domain, Single Forest with Multiple Domains, or Multiple Forests. Each has benefits and concerns, depending on programmatic and organizational structures. The comparison of these three approaches will facilitate almost any Active Directory design effort. Finally, this paper describes some best practices to consider when designing Active Directory based on three years of research and experience.

  15. [Metabolic fitness: physical activity and health].

    PubMed

    Saltin, Bengt; Pilegaard, Henriette

    2002-04-15

    Physical inactivity is strongly associated with an increased risk of premature disease and death, and the falling level of physical activity in Denmark (as in many other countries) makes physical inactivity a major life-style risk factor in many western countries today. Both aerobic fitness (maximum oxygen uptake) and metabolic capacity of the muscles are important in this matter. The present paper focuses on the role of the metabolic capacity/fitness of muscle, because this appears to be especially critical for the development of metabolic-related diseases and thus for the health of the individual. A definition of metabolic fitness is proposed as the ratio between mitochondrial capacity for substrate utilisation and maximum oxygen uptake of the muscle. Indirect means of determining this parameter are discussed. Skeletal muscle is an extraordinarily plastic tissue and metabolic capacity/fitness changes quickly when the level of physical activity is altered. High metabolic fitness includes an elevated use of fat at rest and during exercise. The capacity for glucose metabolism is also enhanced in trained muscle. Some of these adaptations to physical activity are explained. Exercise-induced activation of genes coding for proteins involved in metabolism is described as an underlying mechanism for some of these adaptations. The increased gene expression is of relatively short duration, which implies that a certain regularity of physical activity is required to maintain high metabolic fitness. Thus, metabolic fitness is directly related to how much the muscle is used, but even low levels of physical activity have a beneficial effect on metabolic fitness and the overall health of the individual.

  16. Metabolic activation and inactivation of chemical carcinogens

    SciTech Connect

    Pelkonen, O.; Vaehaekangas, K.

    1980-09-01

    Chemical carcinogens are metabolized by numerous pathways catalyzed by enzymes in endoplasmic reticulum and other parts of the cell. Reactions in which functional groups are created are especially important in the activation of polycyclic hydrocarbon carcinogens to ultimate carcinogenic forms, although other enzymes may also participate in the activation of other chemical carcinogens. The reasons why carcinogens act on specific target tissues are incompletely understood, although differences in enzyme profiles between tissues certainly contribute to the target tissue variability. The concept of metabolic activation of carcinogens by body's own enzymes has led to the development of short-term assay systems, which essentially measure the production of biologically active metabolites from potential carcinogens.

  17. Microbial metabolic activity in soil as measured by dehydrogenase determinations

    NASA Technical Reports Server (NTRS)

    Casida, L. E., Jr.

    1977-01-01

    The dehydrogenase technique for measuring the metabolic activity of microorganisms in soil was modified to use a 6-h, 37 C incubation with either glucose or yeast extract as the electron-donating substrate. The rate of formazan production remained constant during this time interval, and cellular multiplication apparently did not occur. The technique was used to follow changes in the overall metabolic activities of microorganisms in soil undergoing incubation with a limiting concentration of added nutrient. The sequence of events was similar to that obtained by using the Warburg respirometer to measure O2 consumption. However, the major peaks of activity occurred earlier with the respirometer. This possibly is due to the lack of atmospheric CO2 during the O2 consumption measurements.

  18. GM2-ganglioside metabolism in hexosaminidase A deficiency states: determination in situ using labeled GM2 added to fibroblast cultures.

    PubMed Central

    Raghavan, S S; Krusell, A; Krusell, J; Lyerla, T A; Kolodny, E H

    1985-01-01

    To clarify the relationship between hexosaminidase A (HEX A) activity and GM2-ganglioside hydrolysis in atypical clinical situations of HEX A deficiency, we have developed a simple method to assess GM2-ganglioside metabolism in cultured fibroblasts utilizing GM2 labeled with tritium in the sphingosine portion of the molecule. The radioactive lipid is added to the media of cultured skin fibroblasts, and after 10 days the cells are thoroughly washed, then harvested, and their lipid composition analyzed by HPLC. The degree of hydrolysis of the ingested GM2 is determined by comparing the amount of radioactive counts recovered in undegraded substrate with total cellular radioactivity. A deficiency in GM2-ganglioside hydrolysis was demonstrated in seven HEX A-deficient adults with neurological signs and in two healthy-appearing adolescents with older affected siblings. In each case, an analysis of endogenous monosialoganglioside composition revealed an increase in GM2-ganglioside, confirming the presence of a block in the metabolism of GM2. No defect in GM2-catabolism was found in four other healthy individuals with HEX A deficiency. This method of assay is especially helpful in the evaluation of atypical cases of HEX A deficiency for the definitive diagnosis of GM2-gangliosidosis. Images Fig. 1 PMID:2934978

  19. Effects of long-term treatment with pioglitazone on cognition and glucose metabolism of PS1-KI, 3xTg-AD, and wild-type mice

    PubMed Central

    Masciopinto, F; Di Pietro, N; Corona, C; Bomba, M; Pipino, C; Curcio, M; Di Castelnuovo, A; Ciavardelli, D; Silvestri, E; Canzoniero, L MT; Sekler, I; Pandolfi, A; Sensi, S L

    2012-01-01

    In this study, we investigated the effects of long-term (9-month) treatment with pioglitazone (PIO; 20 mg/kg/d) in two animal models of Alzheimer's disease (AD)-related neural dysfunction and pathology: the PS1-KIM146V (human presenilin-1 M146V knock-in mouse) and 3xTg-AD (triple transgenic mouse carrying AD-linked mutations) mice. We also investigated the effects on wild-type (WT) mice. Mice were monitored for body mass changes, fasting glycemia, glucose tolerance, and studied for changes in brain mitochondrial enzyme activity (complexes I and IV) as well as energy metabolism (lactate dehydrogenase (LDH)). Cognitive effects were investigated with the Morris water maze (MWM) test and the object recognition task (ORT). Behavioral analysis revealed that PIO treatment promoted positive cognitive effects in PS1-KI female mice. These effects were associated with normalization of peripheral gluco-regulatory abnormalities that were found in untreated PS1-KI females. PIO-treated PS1-KI females also showed no statistically significant alterations in brain mitochondrial enzyme activity but significantly increased reverse LDH activity.PIO treatment produced no effects on cognition, glucose metabolism, or mitochondrial functioning in 3xTg-AD mice. Finally, PIO treatment promoted enhanced short-term memory performance in WT male mice, a group that did not show deregulation of glucose metabolism but that showed decreased activity of complex I in hippocampal and cortical mitochondria. Overall, these results indicate metabolically driven cognitive-enhancing effects of PIO that are differentially gender-related among specific genotypes. PMID:23254291

  20. Lipid metabolism and potentials of biofuel and high added-value oil production in red algae.

    PubMed

    Sato, Naoki; Moriyama, Takashi; Mori, Natsumi; Toyoshima, Masakazu

    2017-04-01

    Biomass production is currently explored in microalgae, macroalgae and land plants. Microalgal biofuel development has been performed mostly in green algae. In the Japanese tradition, macrophytic red algae such as Pyropia yezoensis and Gelidium crinale have been utilized as food and industrial materials. Researches on the utilization of unicellular red microalgae such as Cyanidioschyzon merolae and Porphyridium purpureum started only quite recently. Red algae have relatively large plastid genomes harboring more than 200 protein-coding genes that support the biosynthetic capacity of the plastid. Engineering the plastid genome is a unique potential of red microalgae. In addition, large-scale growth facilities of P. purpureum have been developed for industrial production of biofuels. C. merolae has been studied as a model alga for cell and molecular biological analyses with its completely determined genomes and transformation techniques. Its acidic and warm habitat makes it easy to grow this alga axenically in large scales. Its potential as a biofuel producer is recently documented under nitrogen-limited conditions. Metabolic pathways of the accumulation of starch and triacylglycerol and the enzymes involved therein are being elucidated. Engineering these regulatory mechanisms will open a possibility of exploiting the full capability of production of biofuel and high added-value oil. In the present review, we will describe the characteristics and potential of these algae as biotechnological seeds.

  1. Metabolic Activity - Skylab Experiment M171

    NASA Technical Reports Server (NTRS)

    1972-01-01

    This chart details Skylab's Metabolic Activity experiment (M171), a medical evaluation facility designed to measure astronauts' metabolic changes while on long-term space missions. The experiment obtained information on astronauts' physiological capabilities and limitations and provided data useful in the design of future spacecraft and work programs. Physiological responses to physical activity was deduced by analyzing inhaled and exhaled air, pulse rate, blood pressure, and other selected variables of the crew while they performed controlled amounts of physical work with a bicycle ergometer. The Marshall Space Flight Center had program responsibility for the development of Skylab hardware and experiments.

  2. Physical activity in obesity and metabolic syndrome.

    PubMed

    Strasser, Barbara

    2013-04-01

    Biological aging is typically associated with a progressive increase in body fat mass and a loss of lean body mass. Owing to the metabolic consequences of reduced muscle mass, it is understood that normal aging and/or decreased physical activity may lead to a higher prevalence of metabolic disorders. Lifestyle modification, specifically changes in diet, physical activity, and exercise, is considered the cornerstone of obesity management. However, for most overweight people it is difficult to lose weight permanently through diet or exercise. Thus, prevention of weight gain is thought to be more effective than weight loss in reducing obesity rates. A key question is whether physical activity can extenuate age-related weight gain and promote metabolic health in adults. Current guidelines suggest that adults should accumulate about 60 minutes of moderate-intensity physical activity daily to prevent unhealthy weight gain. Because evidence suggests that resistance training may promote a negative energy balance and may change body fat distribution, it is possible that an increase in muscle mass after resistance training may be a key mediator leading to better metabolic control.

  3. Meal patterns and meal-induced metabolic changes in calves fed milk ad lib.

    PubMed

    Senn, M; Gross-Lüem, S; Leuenberger, H; Langhans, W

    The feeding behavior of 11 calves fed milk ad lib was characterized and analyzed at the age of 5 weeks, and the short-term changes in the plasma concentrations of various metabolites (glucose, lactate, free fatty acids, triglycerides, beta-hydroxybutyrate) and insulin in relation to a representative spontaneous milk meal were measured during the following week. In a 6-day period, the calves consumed 287 (=86%) of a total of 335 milk meals during the light phase from 0500-2200 [on average, 4.4 +/- 0.5 (mean +/- SEM) meals]. The meal size and duration during light were 2.0 +/- 0.3 kg and 5.3 +/- 0.3 min, respectively. However, only 0.7 +/- 0.1 milk meals of similar size and duration were consumed during the dark phase. The plasma concentrations of insulin and glucose increased in response to the spontaneous milk meal and remained elevated for at least 2 h after meal end. The plasma concentrations of triglycerides, free fatty acids, and beta-hydroxybutyrate also increased after meal termination, and remained elevated until 40 min (triglycerides, free fatty acids) and 60 min (beta-hydroxybutyrate) after meal end, respectively. The observed spontaneous milk intake patterns were similar to the natural suckling behavior described for calves, suggesting that the conditions of the present experiment did not disrupt the animals' natural feeding behavior. Some of the profound metabolic changes in relation to a spontaneous milk meal might contribute to the control of milk intake in calves, but further experiments are necessary to test this idea.

  4. Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism

    PubMed Central

    Kersten, Sander

    2008-01-01

    Plasma lipoproteins are responsible for carrying triglycerides and cholesterol in the blood and ensuring their delivery to target organs. Regulation of lipoprotein metabolism takes place at numerous levels including via changes in gene transcription. An important group of transcription factors that mediates the effect of dietary fatty acids and certain drugs on plasma lipoproteins are the peroxisome proliferator activated receptors (PPARs). Three PPAR isotypes can be distinguished, all of which have a major role in regulating lipoprotein metabolism. PPARα is the molecular target for the fibrate class of drugs. Activation of PPARα in mice and humans markedly reduces hepatic triglyceride production and promotes plasma triglyceride clearance, leading to a clinically significant reduction in plasma triglyceride levels. In addition, plasma high-density lipoprotein (HDL)-cholesterol levels are increased upon PPARα activation in humans. PPARγ is the molecular target for the thiazolidinedione class of drugs. Activation of PPARγ in mice and human is generally associated with a modest increase in plasma HDL-cholesterol and a decrease in plasma triglycerides. The latter effect is caused by an increase in lipoprotein lipase-dependent plasma triglyceride clearance. Analogous to PPARα, activation of PPARβ/δ leads to increased plasma HDL-cholesterol and decreased plasma triglyceride levels. In this paper, a fresh perspective on the relation between PPARs and lipoprotein metabolism is presented. The emphasis is on the physiological role of PPARs and the mechanisms underlying the effect of synthetic PPAR agonists on plasma lipoprotein levels. PMID:18288277

  5. Functions for diverse metabolic activities in heterochromatin

    PubMed Central

    Su, Xue Bessie; Pillus, Lorraine

    2016-01-01

    Growing evidence demonstrates that metabolism and chromatin dynamics are not separate processes but that they functionally intersect in many ways. For example, the lysine biosynthetic enzyme homocitrate synthase was recently shown to have unexpected functions in DNA damage repair, raising the question of whether other amino acid metabolic enzymes participate in chromatin regulation. Using an in silico screen combined with reporter assays, we discovered that a diverse range of metabolic enzymes function in heterochromatin regulation. Extended analysis of the glutamate dehydrogenase 1 (Gdh1) revealed that it regulates silent information regulator complex recruitment to telomeres and ribosomal DNA. Enhanced N-terminal histone H3 proteolysis is observed in GDH1 mutants, consistent with telomeric silencing defects. A conserved catalytic Asp residue is required for Gdh1’s functions in telomeric silencing and H3 clipping. Genetic modulation of α-ketoglutarate levels demonstrates a key regulatory role for this metabolite in telomeric silencing. The metabolic activity of glutamate dehydrogenase thus has important and previously unsuspected roles in regulating chromatin-related processes. PMID:26936955

  6. Functions for diverse metabolic activities in heterochromatin.

    PubMed

    Su, Xue Bessie; Pillus, Lorraine

    2016-03-15

    Growing evidence demonstrates that metabolism and chromatin dynamics are not separate processes but that they functionally intersect in many ways. For example, the lysine biosynthetic enzyme homocitrate synthase was recently shown to have unexpected functions in DNA damage repair, raising the question of whether other amino acid metabolic enzymes participate in chromatin regulation. Using an in silico screen combined with reporter assays, we discovered that a diverse range of metabolic enzymes function in heterochromatin regulation. Extended analysis of the glutamate dehydrogenase 1 (Gdh1) revealed that it regulates silent information regulator complex recruitment to telomeres and ribosomal DNA. Enhanced N-terminal histone H3 proteolysis is observed in GDH1 mutants, consistent with telomeric silencing defects. A conserved catalytic Asp residue is required for Gdh1's functions in telomeric silencing and H3 clipping. Genetic modulation of α-ketoglutarate levels demonstrates a key regulatory role for this metabolite in telomeric silencing. The metabolic activity of glutamate dehydrogenase thus has important and previously unsuspected roles in regulating chromatin-related processes.

  7. Measurement of Ad Libitum Food Intake, Physical Activity, and Sedentary Time in Response to Overfeeding

    PubMed Central

    He, Jianying; Votruba, Susanne; Pomeroy, Jeremy; Bonfiglio, Susan; Krakoff, Jonathan

    2012-01-01

    Given the wide availability of highly palatable foods, overeating is common. Energy intake and metabolic responses to overfeeding may provide insights into weight gain prevention. We hypothesized a down-regulation in subsequent food intake and sedentary time, and up-regulation in non-exercise activity and core temperature in response to overfeeding in order to maintain body weight constant. In a monitored inpatient clinical research unit using a cross over study design, we investigated ad libitum energy intake (EI, using automated vending machines), core body temperature, and physical activity (using accelerometry) following a short term (3-day) weight maintaining (WM) vs overfeeding (OF) diet in healthy volunteers (n = 21, BMI, mean ± SD, 33.2±8.6 kg/m2, 73.6% male). During the ad libitum periods following the WM vs. OF diets, there was no significant difference in mean 3-d EI (4061±1084 vs. 3926±1284 kcal/day, p = 0.41), and there were also no differences either in core body temperature (37.0±0.2°C vs. 37.1±0.2°C, p = 0.75) or sedentary time (70.9±12.9 vs. 72.0±7.4%, p = 0.88). However, during OF (but not WM), sedentary time was positively associated with weight gain (r = 0.49, p = 0.05, adjusted for age, sex, and initial weight). In conclusion, short term overfeeding did not result in a decrease in subsequent ad libitum food intake or overall change in sedentary time although in secondary analysis sedentary time was associated with weight gain during OF. Beyond possible changes in sedentary time, there is minimal attempt to restore energy balance during or following short term overfeeding. Trial Registration ClinicalTrials.gov NCT00342732 PMID:22629311

  8. Metabolic activity of microorganisms in evaporites

    NASA Technical Reports Server (NTRS)

    Rothschild, L. J.; Giver, L. J.; White, M. R.; Mancinelli, R. L.

    1994-01-01

    Crystalline salt is generally considered so hostile to most forms of life that it has been used for centuries as a preservative. Here, we present evidence that prokaryotes inhabiting a natural evaporite crust of halite and gypsum are metabolically active while inside the evaporite for at least 10 months. In situ measurements demonstrated that some of these "endoevaporitic" microorganisms (probably the cyanobacterium Synechococcus Nageli) fixed carbon and nitrogen. Denitrification was not observed. Our results quantified the slow microbial activity that can occur in salt crystals. Implications of this study include the possibility that microorganisms found in ancient evaporite deposits may have been part of an evaporite community.

  9. Metabolic activity of microorganisms in evaporites.

    PubMed

    Rothschild, L J; Giver, L J; White, M R; Mancinelli, R L

    1994-06-01

    Crystalline salt is generally considered so hostile to most forms of life that it has been used for centuries as a preservative. Here, we present evidence that prokaryotes inhabiting a natural evaporite crust of halite and gypsum are metabolically active while inside the evaporite for at least 10 months. In situ measurements demonstrated that some of these "endoevaporitic" microorganisms (probably the cyanobacterium Synechococcus Nageli) fixed carbon and nitrogen. Denitrification was not observed. Our results quantified the slow microbial activity that can occur in salt crystals. Implications of this study include the possibility that microorganisms found in ancient evaporite deposits may have been part of an evaporite community.

  10. Adding diet and exercise counseling to the health promotion plan alleviates anthropometric and metabolic complications in patients with metabolic syndrome.

    PubMed

    Morita-Suzuki, S; Fujioka, Y; Mitsuoka, H; Tashiro, M; Harada, M

    2012-01-01

    We investigated the effects of individual (IC) and group (GC) diet and exercise counseling in men with metabolic syndrome. Participants received exercise instruction and exercise load was monitored. IC participants received individual diet counseling sessions and general consultations at baseline and monthly. GC participants received a group diet counseling session at baseline and general consultations at baseline and monthly. In the IC group, body mass index (BMI) percent body fat, waist circumference, diastolic blood pressure, low-density lipoprotein cholesterol, glycosylated hemoglobin A1c, and liver function levels were reduced significantly after 3 months, whereas in the GC group, waist circumference and levels of liver function were reduced. Exercise load was negatively correlated with change in BMI and waist circumference in the IC group, and positively correlated with changes in high-density lipoprotein cholesterol levels in all subjects and in the GC group. Diet and exercise counseling, especially IC, may benefit patients with metabolic syndrome.

  11. Metabolic assessments during extra-vehicular activity.

    PubMed

    Osipov YuYu; Spichkov, A N; Filipenkov, S N

    1998-01-01

    Extra-vehicular activity (EVA) has a significant role during extended space flights. It demonstrates that humans can survive and perform useful work outside the Orbital Space Stations (OSS) while wearing protective space suits (SS). When the International Space Station 'Alpha' (ISSA) is fully operational, EVA assembly, installation, maintenance and repair operations will become an everyday repetitive work activity in space. It needs new ergonomic evaluation of the work/rest schedule for an increasing of the labor amount per EVA hour. The metabolism assessment is a helpful method to control the productivity of the EVA astronaut and to optimize the work/rest regime. Three following methods were used in Russia to estimate real-time metabolic rates during EVA: 1. Oxygen consumption, computed from the pressure drop in a high pressure bottle per unit time (with actual thermodynamic oxygen properties under high pressure and oxygen leakage taken into account). 2. Carbon dioxide production, computed from CO2 concentration at the contaminant control cartridge and gas flow rate in the life support subsystem closed loop (nominal mode) or gas leakage in the SS open loop (emergency mode). 3. Heat removal, computed from the difference between the temperatures of coolant water or gas and its flow rate in a unit of time (with assumed humidity and wet oxygen state taken into account). Comparison of heat removal values with metabolic rates enables us to determine the thermal balance during an operative medical control of EVA at "Salyut-6", "Salyut-7" and "Mir" OSS. Complex analysis of metabolism, body temperature and heat rate supports a differential diagnosis between emotional and thermal components of stress during EVA. It gives a prognosis of human homeostasis during EVA. Available information has been acquired into an EVA data base which is an effective tool for ergonomical optimization.

  12. Metabolic assessments during extra-vehicular activity

    NASA Astrophysics Data System (ADS)

    Osipov, Yu. Yu.; Spichkov, A. N.; Filipenkov, S. N.

    Extra-vehicular activity (EVA) has a significant role during extended space flights. It demonstrates that humans can survive and perform useful work outside the Orbital Space Stations (OSS) while wearing protective space suits (SS). When the International Space Station 'Alpha'(ISSA) is fully operational, EVA assembly, installation, maintenance and repair operations will become an everyday repetitive work activity in space. It needs new ergonomic evaluation of the work/rest schedule for an increasing of the labor amount per EVA hour. The metabolism assessment is a helpful method to control the productivity of the EVA astronaut and to optimize the work/rest regime. Three following methods were used in Russia to estimate real-time metabolic rates during EVA: 1. Oxygen consumption, computed from the pressure drop in a high pressure bottle per unit time (with actual thermodynamic oxygen properties under high pressure and oxygen leakage taken into account). 2. Carbon dioxide production, computed from CO 2 concentration at the contaminant control cartridge and gas flow rate in the life support subsystem closed loop (nominal mode) or gas leakage in the SS open loop (emergency mode). 3. Heat removal, computed from the difference between the temperatures of coolant water or gas and its flow rate in a unit of time (with assumed humidity and wet oxygen state taken into account). Comparison of heat removal values with metabolic rates enables us to determine the thermal balance during an operative medical control of EVA at "Salyut-6", "Salyut-7" and "Mir" OSS. Complex analysis of metabolism, body temperature and heat rate supports a differential diagnosis between emotional and thermal components of stress during EVA. It gives a prognosis of human homeostasis during EVA. Available information has been acquired into an EVA data base which is an effective tool for ergonomical optimization.

  13. Lipid and fatty acid metabolism in Ralstonia eutropha: relevance for the biotechnological production of value-added products.

    PubMed

    Riedel, Sebastian L; Lu, Jingnan; Stahl, Ulf; Brigham, Christopher J

    2014-02-01

    Lipid and fatty acid metabolism has been well studied in model microbial organisms like Escherichia coli and Bacillus subtilis. The major precursor of fatty acid biosynthesis is also the major product of fatty acid degradation (β-oxidation), acetyl-CoA, which is a key metabolite for all organisms. Controlling carbon flux to fatty acid biosynthesis and from β-oxidation allows for the biosynthesis of natural products of biotechnological importance. Ralstonia eutropha can utilize acetyl-CoA from fatty acid metabolism to produce intracellular polyhydroxyalkanoate (PHA). R. eutropha can also be engineered to utilize fatty acid metabolism intermediates to produce different PHA precursors. Metabolism of lipids and fatty acids can be rerouted to convert carbon into other value-added compounds like biofuels. This review discusses the lipid and fatty acid metabolic pathways in R. eutropha and how they can be used to construct reagents for the biosynthesis of products of industrial importance. Specifically, how the use of lipids or fatty acids as the sole carbon source in R. eutropha cultures adds value to these biotechnological products will be discussed here.

  14. Recent advances in engineering propionyl-CoA metabolism for microbial production of value-added chemicals and biofuels.

    PubMed

    Srirangan, Kajan; Bruder, Mark; Akawi, Lamees; Miscevic, Dragan; Kilpatrick, Shane; Moo-Young, Murray; Chou, C Perry

    2016-08-25

    Diminishing fossil fuel reserves and mounting environmental concerns associated with petrochemical manufacturing practices have generated significant interests in developing whole-cell biocatalytic systems for the production of value-added chemicals and biofuels. Although acetyl-CoA is a common natural biogenic precursor for the biosynthesis of numerous metabolites, propionyl-CoA is unpopular and non-native to most organisms. Nevertheless, with its C3-acyl moiety as a discrete building block, propionyl-CoA can serve as another key biogenic precursor to several biological products of industrial importance. As a result, engineering propionyl-CoA metabolism, particularly in genetically tractable hosts with the use of inexpensive feedstocks, has paved an avenue for novel biomanufacturing. Herein, we present a systematic review on manipulation of propionyl-CoA metabolism as well as relevant genetic and metabolic engineering strategies for microbial production of value-added chemicals and biofuels, including odd-chain alcohols and organic acids, bio(co)polymers and polyketides. [Formula: see text].

  15. Resveratrol inhibits polyphosphoinositide metabolism in activated platelets.

    PubMed

    Olas, Beata; Wachowicz, Barbara; Holmsen, Holm; Fukami, Miriam H

    2005-08-15

    The effects of resveratrol (trans-3,4',5-trihydroxystilbene) on activation responses and the polyphosphoinositide metabolism in human blood platelets have been studied. Resveratrol partially inhibited secretory responses (liberation of dense granule nucleotides and lysosomal acid hydrolases), microparticle formation and protein phosphorylations induced by thrombin. The effects of resveratrol on phosphoinositide metabolites, phosphatidate (PtdOH), phosphatidylinositol (PtdIns), phosphatidylinositol-4-phosphate (PtdIns-4(5)-P), phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P2), phosphatidylinositol-3,4-bisphosphate (PtdIns-3,4-P2) and phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3) were monitored in blood platelets prelabelled with [32P]Pi. Resveratrol not only inhibited the marked increase in levels of PtdOH in platelets activated by thrombin (0.1 U/ml) but it decreased the steady state levels of the other polyphosphoinositide metabolites. The distribution of 32P in phosphoinositides in activated platelets was consistent with inhibition of CDP-DAG inositol transferase and a weak inhibition of PtdIns-4(5)-P kinase. These observations show that resveratrol has a profound effect on phospholipids, particularly on polyphosphoinositide metabolism, and may decrease the amount of PtdIns-4,5-P2 available for signalling in these cells.

  16. Metabolic responses to simulated extravehicular activity

    NASA Technical Reports Server (NTRS)

    Williamson, Rebecca C.; Sharer, Peter J.; Webbon, Bruce W.; Rendon, Lisa R.

    1992-01-01

    Automatic control of the liquid cooling garment (LCG) worn by astronauts during extravehicular activity (EVA) would more efficiently regulate astronaut thermal comfort and improve astronaut productivity. An experiment was conducted in which subjects performed exercise profiles on a unique, supine upper body ergometer to elicit physiological and thermal responses similar to those achieved during zero-g EVAs. Results were analyzed to quantify metabolic rate, various body temperatures, and other heat balance parameters. Such data may lead to development of a microprocessor-based system to automatically maintain astronaut heat balance during extended EVAs.

  17. Apollo experience report: Assessment of metabolic expenditures. [extravehicular activity

    NASA Technical Reports Server (NTRS)

    Waligora, J. M.; Hawkins, W. R.; Humbert, G. F.; Nelson, L. J.; Vogel, S. J.; Kuznetz, L. H.

    1975-01-01

    A significant effort was made to assess the metabolic expenditure for extravehicular activity on the lunar surface. After evaluation of the real-time data available to the flight controller during extravehicular activity, three independent methods of metabolic assessment were chosen based on the relationship between heart rate and metabolic production, between oxygen consumption and metabolic production, and between the thermodynamics of the liquid-cooled garment and metabolic production. The metabolic assessment procedure is analyzed and discussed. Real-time use of this information by the Apollo flight surgeon is discussed. Results and analyses of the Apollo missions and comments concerning future applications are included.

  18. Metabolically active Crenarchaeota in Altamira Cave.

    PubMed

    Gonzalez, Juan M; Portillo, M Carmen; Saiz-Jimenez, Cesareo

    2006-01-01

    Altamira Cave contains valuable paleolithic paintings dating back to 15,000 years. The conservation of these unique paintings is attracting increasing interest, and so, understanding microbial proliferation in Altamira Cave represents a prioritary objective. Here, we show for the first time that members of the Crenarchaeota were metabolically active components of developing microbial communities. RNA was extracted directly from the studied environment, and a number of 16S rRNA gene sequences belonging to the low-temperature Crenarchaeota were detected. Although low-temperature Crenarchaeota detected in a variety of ecosystems by using molecular techniques remain uncultured, this RNA-based study confirms an active participation of the Crenarchaeota in cave biogeochemical cycles.

  19. Metabolically active functional food ingredients for weight control.

    PubMed

    Kovacs, E M R; Mela, D J

    2006-02-01

    The scale of the obesity epidemic creates a pressing consumer need as well as an enormous business opportunity for successful development and marketing of food products with added benefits for weight control. A number of proposed functional food ingredients have been shown to act post-absorptively to influence substrate utilization or thermogenesis. Characteristics and supporting data on conjugated linoleic acid, diglycerides, medium-chain triglycerides, green tea, ephedrine, caffeine, capsaicin and calcium, are reviewed here, giving examples of how these could act to alter energy expenditure or appetite control. Consideration is also given to other factors, in addition to efficacy, which must be satisfied to get such ingredients into foods. We conclude that, for each of the safe, putatively metabolically active agents, there remain gaps in clinical evidence or knowledge of mechanisms, which need to be addressed in order to specify the dietary conditions and food product compositions where these ingredients could be of most benefit for weight control.

  20. Survival of added bacterial species and metabolism of toxic compounds in natural environments

    SciTech Connect

    King, V.M.

    1987-01-01

    Bacteria able to degrade either 2,4-dichlorophenol (DCP) or phenanthrene (PHEN) were isolated from polluted freshwater environments. Two isolates able to degrade each compound were tested for mineralization with a sensitive /sup 14/C assay and for survival in lake water and sewage using a selective medium. One DCP isolate was identified as Alcaligenes paradoxus and the other as Alcaligenes sp. One PHEN isolate was identified as Pseudomonas fluorescens and the other as Pseudomonas sp. All four isolates survived and grew in sterile environments which indicated that starvation would not be a factor in survival of these strains. The number of organisms declined immediately in number in nonsterile lake water. However, they did survive or even grow in nonsterile sewage for a short period before declining in number. Biotic factors appeared to be influential for survival and mineralization of target compounds in many environments. The removal of protozoa, which prey on bacteria, improved survival of the added cells, but had no influence on the mineralization of 10 ..mu..g DCP/L. In comparison, degradation of 10 and 25 mg DCP/L stopped after a few days. Yeast nitrogen base appeared to overcome the lack of nutrient regeneration, a function attributed to protozoa. The additional nutrients increased toxicant mineralization, especially when seeded with appropriate species. Thus, protozoa may limit growth of added cells but appear to be needed for mineralization of higher concentrations of DCP.

  1. Flavor-active esters: adding fruitiness to beer.

    PubMed

    Verstrepen, Kevin J; Derdelinckx, Guy; Dufour, Jean-Pierre; Winderickx, Joris; Thevelein, Johan M; Pretorius, Isak S; Delvaux, Freddy R

    2003-01-01

    As they are responsible for the fruity character of fermented beverages, volatile esters constitute an important group of aromatic compounds in beer. In modern high-gravity fermentations, which are performed in tall cylindroconical vessels, the beer ester balance is often sub-optimal, resulting in a clear decrease in beer quality. Despite the intensive research aimed at unravelling the precise mechanism and regulation of ester synthesis, our current knowledge remains far from complete. However, a number of factors that influence flavor-active ester production have already been described, including wort composition, wort aeration and fermentor design. A thoughtful adaptation of these parameters allows brewers to steer ester concentrations and thus to control the fruity character of their beers. This paper reviews the current knowledge of the biochemistry behind yeast ester synthesis and discusses the different factors that allow ester formation to be controlled during brewery fermentation.

  2. Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals

    PubMed Central

    Bomba, M; Ciavardelli, D; Silvestri, E; Canzoniero, L MT; Lattanzio, R; Chiappini, P; Piantelli, M; Di Ilio, C; Consoli, A; Sensi, S L

    2013-01-01

    Recent studies have shown that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia. Insulin resistance is often associated with T2DM and can induce defective insulin signaling in the central nervous system as well as increase the risk of cognitive impairment in the elderly. Glucagone like peptide-1 (GLP-1) is an incretin hormone and, like GLP-1 analogs, stimulates insulin secretion and has been employed in the treatment of T2DM. GLP-1 and GLP-1 analogs also enhance synaptic plasticity and counteract cognitive deficits in mouse models of neuronal dysfunction and/or degeneration. In this study, we investigated the potential neuroprotective effects of long-term treatment with exenatide, a GLP-1 analog, in two animal models of neuronal dysfunction: the PS1-KI and 3xTg-AD mice. We found that exenatide promoted beneficial effects on short- and long-term memory performances in PS1-KI but not in 3xTg-AD animals. In PS1-KI mice, the drug increased brain lactate dehydrogenase activity leading to a net increase in lactate levels, while no effects were observed on mitochondrial respiration. On the contrary, exenatide had no effects on brain metabolism of 3xTg-AD mice. In summary, our data indicate that exenatide improves cognition in PS1-KI mice, an effect likely driven by increasing the brain anaerobic glycolysis rate. PMID:23640454

  3. Metabolic Activity of Bacteria at High Pressure

    NASA Astrophysics Data System (ADS)

    Picard, A.; Daniel, I.; Oger, P.

    2008-12-01

    a depth of marine sediment of 500 m, or even beneath a water column of 6 km in surface sediments. This suggests that the metabolic activity of surface microorganisms that receive nutrients through sea water percolation into the deeper parts of the sediment, or that sink with the sediment, may represent a significant fraction of the total activity observed in subsurface environments. The present results indicate also that cells in stationary phase at HHP, which preclude growth, can still have a short-term metabolic activity independent of the growth-related activity. Consequently, surface microorganisms have the ability to impact significantly and rapidly on biogeochemical cycles in deep environments.

  4. [Metabolism inhibition stimulates, metabolism activation inhibits cancerogenic activity of ortho-aminoazotoluene in mouse liver].

    PubMed

    Kaledin, V I; Il'nitskaia, S I

    2011-01-01

    Pentachlorophenol, an inhibitor of metabolic activation of aminoazo dyes was administered to suckling mice prior to o-aminoazotoluene (OAT). It was followed by formation of numerous preneoplastic nodules and tumors in the lungs and liver. At the same time, 2,3,7,8-tetrachlorodibenzo-p-dioxine treatment decreased their number in the liver while slightly increasing them in the lung. A possible mechanism of aminoazo dye carcinogenicity is suggested.

  5. Metabolic activity of subsurface life in deep-sea sediments.

    PubMed

    D'Hondt, Steven; Rutherford, Scott; Spivack, Arthur J

    2002-03-15

    Global maps of sulfate and methane in marine sediments reveal two provinces of subsurface metabolic activity: a sulfate-rich open-ocean province, and an ocean-margin province where sulfate is limited to shallow sediments. Methane is produced in both regions but is abundant only in sulfate-depleted sediments. Metabolic activity is greatest in narrow zones of sulfate-reducing methane oxidation along ocean margins. The metabolic rates of subseafloor life are orders of magnitude lower than those of life on Earth's surface. Most microorganisms in subseafloor sediments are either inactive or adapted for extraordinarily low metabolic activity.

  6. Microstructural and phase evolution in metakaolin geopolymers with different activators and added aluminosilicate fillers

    NASA Astrophysics Data System (ADS)

    Sarkar, Madhuchhanda; Dana, Kausik; Das, Sukhen

    2015-10-01

    This work aims to investigate the microstructural and phase evolution of alkali activated metakaolin products with different activators and added aluminosilicate filler phases. The added filler phases have different reactivity to the alkali activated metakaolin system. Microstructural evolution in the alkali activated products has been investigated by X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and Field Emission Scanning Electron Microscope (FESEM). Variation in strength development in alkali activated metakaolin products was followed by compressive strength measurement test. Microstructural study shows that in case of metakaolin with NaOH activator crystalline sodalite formed in all the product samples irrespective of the added filler phases. The microstructure of these NaOH activated products investigated by FESEM showed crystalline and inhomogeneous morphology. Mixed activator containing both NaOH and sodium silicate in a fixed mass ratio formed predominantly amorphous phase. Microstructure of these samples showed more homogeneity than that of NaOH activated metakaolin products. The study further shows that addition of α-Al2O3 powder, non reactive phase to the alkali activated metakaolin system when used in larger amount increased crystalline phase in the matrix. α-Al2O3 powder addition increased the compressive strength of the product samples for both the activator compositions. Added phase of colloidal silica, reactive to the alkali activated metakaolin system when used in larger amount was found to increase amorphous nature of the matrix. Addition of colloidal silica influenced the compressive strength property differently with different activator compositions.

  7. Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis.

    PubMed

    Kasischke, Karl A; Vishwasrao, Harshad D; Fisher, Patricia J; Zipfel, Warren R; Webb, Watt W

    2004-07-02

    We have found that two-photon fluorescence imaging of nicotinamide adenine dinucleotide (NADH) provides the sensitivity and spatial three-dimensional resolution to resolve metabolic signatures in processes of astrocytes and neurons deep in highly scattering brain tissue slices. This functional imaging reveals spatiotemporal partitioning of glycolytic and oxidative metabolism between astrocytes and neurons during focal neural activity that establishes a unifying hypothesis for neurometabolic coupling in which early oxidative metabolism in neurons is eventually sustained by late activation of the astrocyte-neuron lactate shuttle. Our model integrates existing views of brain energy metabolism and is in accord with known macroscopic physiological changes in vivo.

  8. Evidence for metabolic activity of airborne bacteria

    NASA Technical Reports Server (NTRS)

    Chatigny, M. A.; Wolochow, H.

    1974-01-01

    Aerosols of the bacterium Serratia marcescens, and of uniformly labeled C-14 glucose were produced simultaneously and mixed in tubing leading to an aerosol chamber. During a subsequent period of about 5 hrs, carbon dioxide was produced metabolically within the chamber, and labeled material incorporated within the suspended particles first increased then decreased. This constitutes the first direct evidence of microbial metabolism of bacteria suspended in the air.

  9. Controlling self-sustained spiking activity by adding or removing one network link

    NASA Astrophysics Data System (ADS)

    Xu, Kesheng; Huang, Wenwen; Li, Baowen; Dhamala, Mukesh; Liu, Zonghua

    2013-06-01

    Being able to control the neuronal spiking activity in specific brain regions is central to a treatment scheme in several brain disorders such as epileptic seizures, mental depression, and Parkinson's diseases. Here, we present an approach for controlling self-sustained oscillations by adding or removing one directed network link in coupled neuronal oscillators, in contrast to previous approaches of adding stimuli or noise. We find that such networks can exhibit a variety of activity patterns such as on-off switch, sustained spikes, and short-term spikes. We derive the condition for a specific link to be the controller of the on-off effect. A qualitative analysis is provided to facilitate the understanding of the mechanism for spiking activity by adding one link. Our findings represent the first report on generating spike activity with the addition of only one directed link to a network and provide a deeper understanding of the microscopic roots of self-sustained spiking.

  10. An efficient synthesis method targeted to marine alkaloids marinacarbolines A-D and their antitumor activities.

    PubMed

    Li, Jun; Tang, Yang; Jin, Hui-Juan; Cui, Yi-Di; Zhang, Li-Juan; Jiang, Tao

    2015-01-01

    Marinacarbolines A-D are a series of marine β-carboline alkaloids isolated from actinomycete Marinactinospora thermotolerans of the deep South China Sea with antiplasmodial activities. In inhibition assays of in vitro growth of Plasmodium falciparum, marinacarbolines exhibited antiplasmodial activity against drug-sensitive line 3D7 and drug-resistant line Dd2 of P. falciparum. However, approaches for the synthesis of such useful compounds are very limited. In this work, we reported a simple, efficient, and versatile process to synthesize marinacarbolines A-D (1-4). On the basis of that, the antitumor activities of marinacarbolines in a structure-dependent manner were allowed to be unveiled.

  11. Engineering of a Synthetic Metabolic Pathway for the Assimilation of (d)-Xylose into Value-Added Chemicals.

    PubMed

    Cam, Yvan; Alkim, Ceren; Trichez, Debora; Trebosc, Vincent; Vax, Amélie; Bartolo, François; Besse, Philippe; François, Jean Marie; Walther, Thomas

    2016-07-15

    A synthetic pathway for (d)-xylose assimilation was stoichiometrically evaluated and implemented in Escherichia coli strains. The pathway proceeds via isomerization of (d)-xylose to (d)-xylulose, phosphorylation of (d)-xylulose to obtain (d)-xylulose-1-phosphate (X1P), and aldolytic cleavage of the latter to yield glycolaldehyde and DHAP. Stoichiometric analyses showed that this pathway provides access to ethylene glycol with a theoretical molar yield of 1. Alternatively, both glycolaldehyde and DHAP can be converted to glycolic acid with a theoretical yield that is 20% higher than for the exclusive production of this acid via the glyoxylate shunt. Simultaneous expression of xylulose-1 kinase and X1P aldolase activities, provided by human ketohexokinase-C and human aldolase-B, respectively, restored growth of a (d)-xylulose-5-kinase mutant on xylose. This strain produced ethylene glycol as the major metabolic endproduct. Metabolic engineering provided strains that assimilated the entire C2 fraction into the central metabolism or that produced 4.3 g/L glycolic acid at a molar yield of 0.9 in shake flasks.

  12. A computational investigation on radiation damage and activation of structural material for C-ADS

    NASA Astrophysics Data System (ADS)

    Liang, Tairan; Shen, Fei; Yin, Wen; Yu, Quanzhi; Liang, Tianjiao

    2015-11-01

    The C-ADS (China Accelerator-Driven Subcritical System) project, which aims at transmuting high-level radiotoxic waste (HLW) and power generation, is now in the research and development stage. In this paper, a simplified ADS model is set up based on the IAEA Th-ADS benchmark calculation model, then the radiation damage as well as the residual radioactivity of the structural material are estimated using the Monte Carlo simulation method. The peak displacement production rate, gas productions, activity and residual dose rate of the structural components like beam window and outer casing of subcritical reactor core are calculated. The calculation methods and the corresponding results provide the basic reference for making reasonable predictions for the lifetime and maintenance operations of the structural material of C-ADS.

  13. Recombinant Ad35 adenoviral proteins as potent modulators of human T-cell activation

    PubMed Central

    Hay, Joanne; Carter, Darrick; Lieber, André; Astier, Anne L

    2015-01-01

    The protein CD46 protects cells from complement attack by regulating cleavage of C3b and C3d. CD46 also regulates the adaptive immune response by controlling T-cell activation and differentiation. Co-engagement of the T-cell receptor and CD46 notably drives T-cell differentiation by switching production of interferon-γ to secretion of anti-inflammatory interleukin-10. This regulatory pathway is altered in several chronic inflammatory diseases, highlighting its key role for immune homeostasis. The manipulation of the CD46 pathway may therefore provide a powerful means to regulate immune responses. Herein, we investigated the effect of recombinant proteins derived from the fibre knob of the adenovirus serotype 35 (Ad35) that uses CD46 as its entry receptor, on human T-cell activation. We compared the effects of Ad35K++, engineered to exhibit enhanced affinity to CD46, and of Ad35K−, mutated in the binding site for CD46. Ad35K++ profoundly affects T-cell activation by decreasing the levels of CD46 at the surface of primary T cells, and impairing T-cell co-activation, shown by decreased CD25 expression, reduced proliferation and lower secretion of interleukin-10 and interferon-γ. In contrast, Ad35K− acts a potent co-activator of T cells, enhancing T-cell proliferation and cytokine production. These data show that recombinant Ad35 proteins are potent modulators of human T-cell activation, and support their further development as potential drugs targeting T-cell responses. PMID:25251258

  14. Obesity, Metabolic Syndrome, and Physical Activity.

    ERIC Educational Resources Information Center

    Yeater, Rachel

    2000-01-01

    Discusses the scope of the problem of obesity in the United States, noting the health risks associated with being overweight or obese (e.g., gallstones, osteoarthritis, sleep apnea, and colon cancer); discussing the association of type-II diabetes mellitus with obesity; examining the effects of exercise on metabolic disease; and looking at…

  15. Recovery from activity-stress ulcer by ad lib feeding in rats.

    PubMed

    Hirao, M; Tanaka, M; Emoto, H; Ishii, H; Yokoo, H; Yoshida, M; Tsuda, A

    1997-12-31

    In order to investigate the recovery from activity-stress ulcers by ad lib-feeding and/or cessation of running, male Wistar rats were exposed to the activity-stress paradigm, and the rats that revealed hypothermia (their rectal temperature fell below 36 degrees C) were sacrificed either immediately or after several 24 h periods of healing. Rats that were sacrificed immediately after the appearance of hypothermia and those that were exposed to restricted feeding plus cessation of running revealed severe activity-stress ulcers, whereas few ulcers were observed in rats given ad lib-feeding and those that were given ad lib-feeding plus cessation of running. Although no significant differences in relative weights of spleen and thymus were obtained among the different recovery conditions, the relative weights of the adrenal glands were highest in the restricted feeding plus cessation of running group, whereas, the other animals exposed to the activity-stress paradigm showed no differences. These results indicate that activity-stress ulcers recover under conditions of ad lib-feeding within 24 h, but they are not influenced by cessation of running. These data also suggest that organ weights are not affected by any manipulations employed in the present study.

  16. Physical activity and metabolic syndrome in liver transplant recipients.

    PubMed

    Kallwitz, Eric R; Loy, Veronica; Mettu, Praveen; Von Roenn, Natasha; Berkes, Jamie; Cotler, Scott J

    2013-10-01

    There is a high prevalence of metabolic syndrome in liver transplant recipients, a population that tends to be physically inactive. The aim of this study was to characterize physical activity and evaluate the relationship between physical activity and metabolic syndrome after liver transplantation. A cross-sectional analysis was performed in patients more than 3 months after transplantation. Metabolic syndrome was classified according to National Cholesterol Education Panel Adult Treatment Panel III guidelines. Physical activity, including duration, frequency, and metabolic equivalents of task (METs), was assessed. The study population consisted of 204 subjects, with 156 more than 1 year after transplantation. The median time after transplantation was 53.5 months (range = 3-299 months). The mean duration of exercise was 90 ± 142 minutes, and the mean MET score was 3.6 ± 1.5. Metabolic syndrome was observed in 58.8% of all subjects and in 63.5% of the subjects more than 1 year after transplantation. In a multivariate analysis involving all subjects, metabolic syndrome was associated with a time after transplantation greater than 1 year [odds ratio (OR) = 2.909, 95% confidence interval (CI) = 1.389-6.092] and older age (OR = 1.036, 95% CI = 1.001-1.072). A second analysis was performed for only patients more than 1 year after transplantation. In a multivariate analysis, metabolic syndrome was associated with lower exercise intensity (OR = 0.690, 95% CI = 0.536-0.887), older age (OR = 1.056, 95% CI = 1.014-1.101), and pretransplant diabetes (OR = 4.246, 95% CI = 1.300-13.864). In conclusion, metabolic syndrome is common after liver transplantation, and the rate is significantly higher in patients more than 1 year after transplantation. The observation that exercise intensity is inversely related to metabolic syndrome after transplantation is novel and suggests that physical activity might provide a means for reducing metabolic syndrome complications in liver

  17. Calcium-dependent activation of mitochondrial metabolism in mammalian cells

    PubMed Central

    Gaspers, Lawrence D.; Thomas, Andrew P.

    2008-01-01

    Endogenous fluorophores provide a simple, but elegant means to investigate the relationship between agonist-evoked Ca2+ signals and the activation of mitochondrial metabolism. In this article, we discuss the methods and strategies to measure cellular pyridine nucleotide and flavoprotein fluorescence alone or in combination with Ca2+-sensitive indicators. These methods were developed using primary cultured hepatocytes and neurons, which contain relatively high levels of endogenous fluorophores and robust metabolic responses. Nevertheless, these methods are amendable to a wide variety of primary cell types and cell lines that maintain active mitochondrial metabolism. PMID:18854213

  18. Chemoprotective activity of boldine: modulation of drug-metabolizing enzymes.

    PubMed

    Kubínová, R; Machala, M; Minksová, K; Neca, J; Suchý, V

    2001-03-01

    Possible chemoprotective effects of the naturally occurring alkaloid boldine, a major alkaloid of boldo (Peumus boldus Mol.) leaves and bark, including in vitro modulations of drug-metabolizing enzymes in mouse hepatoma Hepa-1 cell line and mouse hepatic microsomes, were investigated. Boldine manifested inhibition activity on hepatic microsomal CYP1A-dependent 7-ethoxyresorufin O-deethylase and CYP3A-dependent testosterone 6 beta-hydroxylase activities and stimulated glutathione S-transferase activity in Hepa-1 cells. In addition to the known antioxidant activity, boldine could decrease the metabolic activation of other xenobiotics including chemical mutagens.

  19. Functional modules, structural topology, and optimal activity in metabolic networks.

    PubMed

    Resendis-Antonio, Osbaldo; Hernández, Magdalena; Mora, Yolanda; Encarnación, Sergio

    2012-01-01

    Modular organization in biological networks has been suggested as a natural mechanism by which a cell coordinates its metabolic strategies for evolving and responding to environmental perturbations. To understand how this occurs, there is a need for developing computational schemes that contribute to integration of genomic-scale information and assist investigators in formulating biological hypotheses in a quantitative and systematic fashion. In this work, we combined metabolome data and constraint-based modeling to elucidate the relationships among structural modules, functional organization, and the optimal metabolic phenotype of Rhizobium etli, a bacterium that fixes nitrogen in symbiosis with Phaseolus vulgaris. To experimentally characterize the metabolic phenotype of this microorganism, we obtained the metabolic profile of 220 metabolites at two physiological stages: under free-living conditions, and during nitrogen fixation with P. vulgaris. By integrating these data into a constraint-based model, we built a refined computational platform with the capability to survey the metabolic activity underlying nitrogen fixation in R. etli. Topological analysis of the metabolic reconstruction led us to identify modular structures with functional activities. Consistent with modular activity in metabolism, we found that most of the metabolites experimentally detected in each module simultaneously increased their relative abundances during nitrogen fixation. In this work, we explore the relationships among topology, biological function, and optimal activity in the metabolism of R. etli through an integrative analysis based on modeling and metabolome data. Our findings suggest that the metabolic activity during nitrogen fixation is supported by interacting structural modules that correlate with three functional classifications: nucleic acids, peptides, and lipids. More fundamentally, we supply evidence that such modular organization during functional nitrogen fixation is

  20. Inuloxins A-D and derivatives as antileishmanial agents: structure-activity relationship study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inuloxins A-D (1-4) and a-costic acid (5), the phytotoxic compounds previously isolated from Inula viscosa, as well as synthetic derivatives of inuloxin A (compounds 6-10), inuloxin C (compound 11) and inuloxin D (compound 12) were tested in vitro for their activity against Leishmania donovani, the ...

  1. Metabolic activity, experiment M171. [space flight effects on human metabolism

    NASA Technical Reports Server (NTRS)

    Michel, E. L.; Rummel, J. A.

    1973-01-01

    The Skylab metabolic activity experiment determines if man's metabolic effectiveness in doing mechanical work is progressively altered by a simulated Skylab environment, including environmental factors such as slightly increased pCO2. This test identified several hardware/procedural anomalies. The most important of these were: (1) the metabolic analyzer measured carbon dioxide production and expired water too high; (2) the ergometer load module failed under continuous high workload conditions; (3) a higher than desirable number of erroneous blood pressure measurements were recorded; (4) vital capacity measurements were unreliable; and (5) anticipated crew personal exercise needs to be more structured.

  2. Activating transcription factor 3 regulates immune and metabolic homeostasis.

    PubMed

    Rynes, Jan; Donohoe, Colin D; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek; Uhlirova, Mirka

    2012-10-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins.

  3. Amyloid-β Oligomers Transiently Inhibit AMP-activated kinase and Cause Metabolic Defects in Hippocampal Neurons.

    PubMed

    Seixas da Silva, Gisele S; Melo, Helen M; Lourenco, Mychael V; Lyra E Silva, Natalia de M; de Carvalho, Marcelo B; Alves-Leon, Soniza; de Souza, Jorge M; Klein, William L; da-Silva, Wagner S; Ferreira, Sergio T; De Felice, Fernanda G

    2017-03-16

    AMP-activated kinase (AMPK) is a key player in energy sensing and metabolic reprogramming under cellular energy restriction. Several studies have linked impaired AMPK function to peripheral metabolic diseases such as diabetes. However, the impact of neurological disorders, such as Alzheimer disease (AD), on AMPK function and downstream effects of altered AMPK activity on neuronal metabolism have been investigated only recently. Here, we report the impact of A β oligomers (AβOs), synaptotoxins that accumulate in AD brains, on neuronal AMPK activity. Short-term exposure of cultured rat hippocampal neurons or ex vivo human cortical slices to AβOs transiently decreased intracellular ATP levels and AMPK activity, as evaluated by its phosphorylation at threonine residue 172 (AMPKpThr172). The AβO-dependent reduction in AMPKpThr172 levels was mediated by glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype, and resulted in removal of glucose transporters (GLUTs) from the surfaces of dendritic processes in hippocampal neurons. Importantly, insulin prevented the AβO-induced inhibition of AMPK. Our results establish a novel toxic impact of A βOs on neuronal metabolism and suggest that AβO-induced, NMDA receptor-mediated AMPK inhibition may play a key role in early brain metabolic defects in AD.

  4. Anatomical Grading for Metabolic Activity of Brown Adipose Tissue

    PubMed Central

    Becker, Anton S.; Nagel, Hannes W.; Wolfrum, Christian; Burger, Irene A.

    2016-01-01

    Background Recent advances in obesity research suggest that BAT activity, or absence thereof, may be an important factor in the growing epidemic of obesity and its manifold complications. It is thus important to assess larger populations for BAT-activating and deactivating factors. 18FDG-PET/CT is the standard method to detect and quantify metabolic BAT activity, however, the manual measurement is not suitable for large studies due to its time-consuming nature and poor reproducibility across different software and devices. Methodology/Main Findings In a retrospective study, 1060 consecutive scans of 1031 patients receiving a diagnostic 18FDG-PET/CT were examined for the presence of active BAT. Patients were classified according to a 3-tier system (supraclavicular, mediastinal, infradiaphragmatic) depending on the anatomical location of their active BAT depots, with the most caudal location being the decisive factor. The metabolic parameters (maximum activity, total volume and total glycolysis) were measured on a standard PET/CT workstation. Mean age of the population was 60±14.6y. 41.61% of patients were female. Metabolically active BAT was found in 53 patients (5.1%). Female, younger and leaner patients tended to have more active BAT, higher metabolic activity and more caudally active BAT. In total, 15 patients showed only supraclavicular, 27 additional mediastinal, and 11 infradiaphragmal activity. Interestingly, the activation of BAT always followed a cranio-caudal gradient. This anatomical pattern correlated with age and BMI as well as with all metabolic parameters, including maximum and total glycolysis (p<0.001). Conclusion Based on our data we propose a simple method to grade or quantify the degree of BAT amount/activity in patients based on the most caudally activated depot. As new modalities for BAT visualization may arise in the future, this system would allow direct comparability with other modalities, in contrary to the PET-metrics, which are

  5. Effects of adding fluids to solid foods on muscle activity and number of chewing cycles.

    PubMed

    van der Bilt, Andries; Engelen, Lina; Abbink, Jan; Pereira, Luciano J

    2007-06-01

    The production of a sufficient amount of saliva is indispensable for good chewing. In the present study, we examined the hypothesis that adding fluid to a food will facilitate the chewing process, especially for dry foods. The effect might be larger for subjects with relatively low salivary flow rates. Furthermore, adding fluids that contain mucins or alpha-amylase may have a larger facilitating effect on mastication than the addition of water alone. Twenty subjects chewed on melba toast, breakfast cake, carrot, peanut, and Gouda cheese. In addition, they chewed on these foods after different volumes of water, artificial saliva containing mucins, or a solution of alpha-amylase had been added. Muscle activity and number of chewing strokes until swallowing were measured. The salivary flow rates of the subjects were also determined. Adding fluid to the food significantly reduced the number of chewing cycles and total muscular work (i.e. the integrated surface electromyograpy of masseter and temporalis muscles measured bilaterally, summed for all chewing cycles) until swallowing for all foods, except carrot. The largest effects were observed for melba and cake, which are dry products requiring sufficient saliva to form a coherent bolus safe for swallowing. More facilitation of the chewing process was observed after adding fluid to breakfast cake for subjects with relatively low salivary flow rates. The type of fluid had no significant effect on the chewing process.

  6. Peroxisome Proliferators-Activated Receptor (PPAR) Modulators and Metabolic Disorders

    PubMed Central

    Cho, Min-Chul; Lee, Kyoung; Paik, Sang-Gi; Yoon, Do-Young

    2008-01-01

    Overweight and obesity lead to an increased risk for metabolic disorders such as impaired glucose regulation/insulin resistance, dyslipidemia, and hypertension. Several molecular drug targets with potential to prevent or treat metabolic disorders have been revealed. Interestingly, the activation of peroxisome proliferator-activated receptor (PPAR), which belongs to the nuclear receptor superfamily, has many beneficial clinical effects. PPAR directly modulates gene expression by binding to a specific ligand. All PPAR subtypes (α, γ, and σ) are involved in glucose metabolism, lipid metabolism, and energy balance. PPAR agonists play an important role in therapeutic aspects of metabolic disorders. However, undesired effects of the existing PPAR agonists have been reported. A great deal of recent research has focused on the discovery of new PPAR modulators with more beneficial effects and more safety without producing undesired side effects. Herein, we briefly review the roles of PPAR in metabolic disorders, the effects of PPAR modulators in metabolic disorders, and the technologies with which to discover new PPAR modulators. PMID:18566691

  7. The HOMA-Adiponectin (HOMA-AD) Closely Mirrors the HOMA-IR Index in the Screening of Insulin Resistance in the Brazilian Metabolic Syndrome Study (BRAMS)

    PubMed Central

    Cassani, Roberta Soares Lara; Forti, Adriana Costa e; Pareja, José Carlos; Tambascia, Marcos Antonio; Geloneze, Bruno

    2016-01-01

    Background The major adverse consequences of obesity are associated with the development of insulin resistance (IR) and adiposopathy. The Homeostasis Model Assessment-Adiponectin (HOMA-AD) was proposed as a modified version of the HOMA1-IR, which incorporates adiponectin in the denominator of the index. Objectives To evaluate the performance of the HOMA-AD index compared with the HOMA1-IR index as a surrogate marker of IR in women, and to establish the cutoff value of the HOMA-AD. Subjects/Methods The Brazilian Metabolic Syndrome Study (BRAMS) is a cross-sectional multicenter survey. The data from 1,061 subjects met the desired criteria: 18–65 years old, BMI: 18.5–49.9 Kg/m² and without diabetes. The IR was assessed by the indexes HOMA1-IR and HOMA-AD (total sample) and by the hyperglycemic clamp (n = 49). Metabolic syndrome was defined using the IDF criteria. Results For the IR assessed by the clamp, the HOMA-AD demonstrated a stronger coefficient of correlation (r = -0.64) compared with the HOMA1-IR (r = -0.56); p < 0.0001. In the ROC analysis, compared with the HOMA1-IR, the HOMA-AD showed higher values of the AUC for the identification of IR based on the clamp test (AUC: 0.844 vs. AUC: 0.804) and on the metabolic syndrome (AUC: 0.703 vs. AUC: 0.689), respectively; p < 0.001 for all. However, the pairwise comparison did not show evidence of superiority for the HOMA-AD in comparison with the HOMA1-IR in the diagnosis of IR and metabolic syndrome (p > 0.05). The optimal cutoff identified for the HOMA-AD for the diagnosis of IR was 0.95. Conclusions The HOMA-AD index was demonstrated to be a useful surrogate marker for detecting IR among adult women and presented a similar performance compared with the HOMA1-IR index. These results may assist physicians and researchers in determining which method to use to evaluate IR in light of the available facilities. PMID:27490249

  8. Species diversity and metabolic impact of the microbiota are low in spontaneously acidified Belgian sausages with an added starter culture of Staphylococcus carnosus.

    PubMed

    Janssens, M; Myter, N; De Vuyst, L; Leroy, F

    2012-04-01

    Quality of fermented sausages is affected by acidifying lactic acid bacteria (LAB) and colour- and flavour-promoting coagulase-negative staphylococci (CNS), whether or not used as starter culture. Artisan fermented sausages are often perceived as superior to industrial variants, partially because of the specific microbiota due to spontaneous acidification, which may be considered as an artisan characteristic. Therefore, two kinds of spontaneously acidified Belgian sausages were prepared (Belgian-type salami and Boulogne sausage), but with addition of a Staphylococcus carnosus culture. The Belgian-type salami was made from pork and beef, whereas the Boulogne sausage contained pork and horse meat. In all cases, Lactobacillus sakei was the dominant LAB species present on the raw materials and during fermentation, whereas enterococci remained present in the background. Enterobacteriaceae vanished after fermentation. The CNS species diversity on the raw materials was large and differed between the pork, beef, and horse meat. Nevertheless, this species diversity was annihilated during fermentation by the added S. carnosus culture. The volatiles fraction was mainly composed of aldehydes that originated from lipid oxidation and spices-derived compounds. Aromatic compounds that are typically associated to CNS activity, such as end-products from the metabolism of branched-chain amino acids, were not present in the Belgian-type salami and only marginally present in the Boulogne sausage. In conclusion, spontaneous acidification of Belgian-type fermented sausages leads to dominance of L. sakei and is no guarantee for bacterial contribution to the aroma profile when S. carnosus is added as a starter culture.

  9. Ionizing Radiation Impairs T Cell Activation by Affecting Metabolic Reprogramming.

    PubMed

    Li, Heng-Hong; Wang, Yi-Wen; Chen, Renxiang; Zhou, Bin; Ashwell, Jonathan D; Fornace, Albert J

    2015-01-01

    Ionizing radiation has a variety of acute and long-lasting adverse effects on the immune system. Whereas measureable effects of radiation on immune cell cytotoxicity and population change have been well studied in human and animal models, little is known about the functional alterations of the surviving immune cells after ionizing radiation. The objective of this study was to delineate the effects of radiation on T cell function by studying the alterations of T cell receptor activation and metabolic changes in activated T cells isolated from previously irradiated animals. Using a global metabolomics profiling approach, for the first time we demonstrate that ionizing radiation impairs metabolic reprogramming of T cell activation, which leads to substantial decreases in the efficiency of key metabolic processes required for activation, such as glucose uptake, glycolysis, and energy metabolism. In-depth understanding of how radiation impacts T cell function highlighting modulation of metabolism during activation is not only a novel approach to investigate the pivotal processes in the shift of T cell homeostasis after radiation, it also may lead to new targets for therapeutic manipulation in the combination of radiotherapy and immune therapy. Given that appreciable effects were observed with as low as 10 cGy, our results also have implications for low dose environmental exposures.

  10. Ethanol Metabolism Activates Cell Cycle Checkpoint Kinase, Chk2

    PubMed Central

    Clemens, Dahn L.; Mahan Schneider, Katrina J.; Nuss, Robert F.

    2011-01-01

    Chronic ethanol abuse results in hepatocyte injury and impairs hepatocyte replication. We have previously shown that ethanol metabolism results in cell cycle arrest at the G2/M transition, which is partially mediated by inhibitory phosphorylation of the cyclin-dependent kinase, Cdc2. To further delineate the mechanisms by which ethanol metabolism mediates this G2/M arrest, we investigated the involvement of upstream regulators of Cdc2 activity. Cdc2 is activated by the phosphatase Cdc25C. The activity of Cdc25C can, in turn, be regulated by the checkpoint kinase, Chk2, which is regulated by the kinase ataxia telangiectasia mutated (ATM). To investigate the involvement of these regulators of Cdc2 activity, VA-13 cells, which are Hep G2 cells modified to efficiently express alcohol dehydrogenase, were cultured in the presence or absence of 25 mM ethanol. Immunoblots were performed to determine the effects of ethanol metabolism on the activation of Cdc25C, Chk2, and ATM. Ethanol metabolism increased the active forms of ATM, and Chk2, as well as the phosphorylated form of Cdc25C. Additionally, inhibition of ATM resulted in approximately 50% of the cells being rescued from the G2/M cell cycle arrest, and ameliorated the inhibitory phosphorylation of Cdc2. Our findings demonstrate that ethanol metabolism activates ATM. ATM can activate the checkpoint kinase Chk2, resulting in phosphorylation of Cdc25C, and ultimately in the accumulation of inactive Cdc2. This may, in part, explain the ethanol metabolism-mediated impairment in hepatocyte replication, which may be important in the initiation and progression of alcoholic liver injury. PMID:21924579

  11. Physical Activity, Metabolic Syndrome, and Overweight in Rural Youth

    ERIC Educational Resources Information Center

    Moore, Justin B.; Davis, Catherine L.; Baxter, Suzanne Domel; Lewis, Richard D.; Yin, Zenong

    2008-01-01

    Background: Research suggests significant health differences between rural dwelling youth and their urban counterparts with relation to cardiovascular risk factors. This study was conducted to (1) determine relationships between physical activity and markers of metabolic syndrome, and (2) to explore factors relating to physical activity in a…

  12. Linking neuronal brain activity to the glucose metabolism

    PubMed Central

    2013-01-01

    Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. Methods First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Results Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. Conclusions The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported. PMID:23988084

  13. An Optimal CDS Construction Algorithm with Activity Scheduling in Ad Hoc Networks.

    PubMed

    Penumalli, Chakradhar; Palanichamy, Yogesh

    2015-01-01

    A new energy efficient optimal Connected Dominating Set (CDS) algorithm with activity scheduling for mobile ad hoc networks (MANETs) is proposed. This algorithm achieves energy efficiency by minimizing the Broadcast Storm Problem [BSP] and at the same time considering the node's remaining energy. The Connected Dominating Set is widely used as a virtual backbone or spine in mobile ad hoc networks [MANETs] or Wireless Sensor Networks [WSN]. The CDS of a graph representing a network has a significant impact on an efficient design of routing protocol in wireless networks. Here the CDS is a distributed algorithm with activity scheduling based on unit disk graph [UDG]. The node's mobility and residual energy (RE) are considered as parameters in the construction of stable optimal energy efficient CDS. The performance is evaluated at various node densities, various transmission ranges, and mobility rates. The theoretical analysis and simulation results of this algorithm are also presented which yield better results.

  14. Cooperative enhancement of deoxyribozyme activity by chemical modification and added cationic copolymer

    PubMed Central

    Saito, Ken; Shimada, Naohiko; Maruyama, Atushi

    2016-01-01

    Abstract Deoxyribozymes (DNAzymes) having RNA-cleaving activity have widely been explored as tools for therapeutic and diagnostic purposes. Both the chemical cleaving step and the turnover step should be improved for enhancing overall activity of DNAzymes. We have shown that cationic copolymer enhanced DNAzyme activity by increasing turnover efficacy. In this paper, effects of the copolymer on DNAzymes modified with locked nucleic acids (LNA) or 2′-O-methylated (2′-OMe) nucleic acids were studied. The copolymer increased activity of these chemically modified DNAzymes. More than 30-fold enhancement in multiple-turnover catalytic activity was observed with 2′-OMe-modified DNAzyme in the presence of the copolymer. DNAzyme catalytic activity was successfully enhanced by cooperation of the added copolymer and chemical modification of DNAzyme. PMID:27877894

  15. STAT3 Activities and Energy Metabolism: Dangerous Liaisons

    PubMed Central

    Camporeale, Annalisa; Demaria, Marco; Monteleone, Emanuele; Giorgi, Carlotta; Wieckowski, Mariusz R.; Pinton, Paolo; Poli, Valeria

    2014-01-01

    STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3C/C) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3C/C MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3C/C MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms. PMID:25089666

  16. Influence of physical activity to bone metabolism.

    PubMed

    Drenjančević, Ines; Davidović Cvetko, Erna

    2013-02-01

    Bone remodeling is a lifetime process. Peak bone mass is achieved in the twenties, and that value is very important for skeleton health in older years of life. Modern life style with its diet poor in nutrients, and very low intensity of physical activity negatively influences health in general, and bone health as well. Bones are adapting to changes in load, so applying mechanical strain to bones results in greater bone mass and hardness. That makes physical activity important in maintaining skeleton health. Numerous studies confirm good influence of regular exercising to bone health, and connection of physical activity in youth to better bone density in older age. To activate bone remodeling mechanisms, it is necessary to apply mechanical strain to bones by exercise. Considering global problem of bone loss and osteoporosis new ways of activating young people to practice sports and active stile of life are necessary to maintain skeleton health and health in general. This paper aims to review physiological mechanisms of bone remodeling that are influenced by physical exercise.

  17. Characterization of Alcaligenes faecalis strain AD15 indicating biocontrol activity against plant pathogens.

    PubMed

    Yokoyama, Shin-ichiro; Adachi, Yoshitomi; Asakura, Shuichi; Kohyama, Erina

    2013-01-01

    Bacterial strain possessing both bacteriostatic and fungistatic activity (biocontrol activity) against pathogens of cyclamen (Cyclamen sp.) was isolated from the soil in Gifu Prefecture, Japan, and characterized with respect to its taxonomic and biocontrol properties. The sequence of its 16S rRNA gene, morphology, biochemistry, and fatty acid composition demonstrated that it is a strain most closely related to Alcaligenes faecalis subsp. faecalis LMG 1229(T). The isolate was named A. faecalis strain AD15. A. faecalis AD15 produced hydroxylamine at maximum yields of 33.3±1.7 mg/L after 16 h cultivation in LB medium and 19.0±0.44 mg/L after 19 h cultivation in synthetic medium. Moreover, minimum inhibitory concentrations of hydroxylamine against the cyclamen pathogens Pantoea agglomerans and Colletotrichum gloeosporioides were 4.20±0.98 and 16.5±0.67 mg/L. These results indicated that the biocontrol activity of strain AD15 might be attributed to hydroxylamine, a metabolite in the culture medium, and it had the potential for biopesticide application.

  18. Glutamate and GABA-metabolizing enzymes in post-mortem cerebellum in Alzheimer's disease: phosphate-activated glutaminase and glutamic acid decarboxylase.

    PubMed

    Burbaeva, G Sh; Boksha, I S; Tereshkina, E B; Savushkina, O K; Prokhorova, T A; Vorobyeva, E A

    2014-10-01

    Enzymes of glutamate and GABA metabolism in postmortem cerebellum from patients with Alzheimer's disease (AD) have not been comprehensively studied. The present work reports results of original comparative study on levels of phosphate-activated glutaminase (PAG) and glutamic acid decarboxylase isoenzymes (GAD65/67) in autopsied cerebellum samples from AD patients and matched controls (13 cases in each group) as well as summarizes published evidence for altered levels of PAG and GAD65/67 in AD brain. Altered (decreased) levels of these enzymes and changes in links between amounts of these enzymes and other glutamate-metabolizing enzymes (such as glutamate dehydrogenase and glutamine synthetase-like protein) in AD cerebella suggest significantly impaired glutamate and GABA metabolism in this brain region, which was previously regarded as not substantially involved in AD pathogenesis.

  19. Effects of activation of endocannabinoid system on myocardial metabolism.

    PubMed

    Polak, Agnieszka; Harasim, Ewa; Chabowski, Adrian

    2016-05-21

    Endocannabinoids exert their effect on the regulation of energy homeostasis via activation of specific receptors. They control food intake, secretion of insulin, lipids and glucose metabolism, lipid storage. Long chain fatty acids are the main myocardial energy substrate. However, the heart exerts enormous metabolic flexibility emphasized by its ability to utilzation not only fatty acids, but also glucose, lactate and ketone bodies. Endocannabinoids can directly act on the cardiomyocytes through the CB1 and CB2 receptors present in cardiomyocytes. It appears that direct activation of CB1 receptors promotes increased lipogenesis, pericardial steatosis and bioelectrical dysfunction of the heart. In contrast, stimulation of CB2 receptors exhibits cardioprotective properties, helping to maintain appropriate amount of ATP in cardiomyocytes. Furthermore, the effects of endocannabinoids at both the central nervous system and peripheral tissues, such as liver, pancreas, or adipose tissue, resulting indirectly in plasma availability of energy substrates and affects myocardial metabolism. To date, there is little evidence that describes effects of activation of the endocannabinoid system in the cardiovascular system under physiological conditions. In the present paper the impact of metabolic diseases, i. e. obesity and diabetes, as well as the cardiovascular diseases - hypertension, myocardial ischemia and myocardial infarction on the deregulation of the endocannabinoid system and its effect on the metabolism are described.

  20. Metabolic activation of benzodiazepines by CYP3A4.

    PubMed

    Mizuno, Katsuhiko; Katoh, Miki; Okumura, Hirotoshi; Nakagawa, Nao; Negishi, Toru; Hashizume, Takanori; Nakajima, Miki; Yokoi, Tsuyoshi

    2009-02-01

    Cytochrome P450 3A4 is the predominant isoform in liver, and it metabolizes more than 50% of the clinical drugs commonly used. However, CYP3A4 is also responsible for metabolic activation of drugs, leading to liver injury. Benzodiazepines are widely used as hypnotics and sedatives for anxiety, but some of them induce liver injury in humans. To clarify whether benzodiazepines are metabolically activated, 14 benzodiazepines were investigated for their cytotoxic effects on HepG2 cells treated with recombinant CYP3A4. By exposure to 100 microM flunitrazepam, nimetazepam, or nitrazepam, the cell viability in the presence of CYP3A4 decreased more than 25% compared with that of the control. In contrast, in the case of other benzodiazepines, the changes in the cell viability between CYP3A4 and control Supersomes were less than 10%. These results suggested that nitrobenzodiazepines such as flunitrazepam, nimetazepam, and nitrazepam were metabolically activated by CYP3A4, which resulted in cytotoxicity. To identify the reactive metabolite, the glutathione adducts of flunitrazepam and nimetazepam were investigated by liquid chromatography-tandem mass spectrometry. The structural analysis for the glutathione adducts of flunitrazepam indicated that a nitrogen atom in the side chain of flunitrazepam was conjugated with the thiol of glutathione. Therefore, the presence of a nitro group in the side chain of benzodiazepines may play a crucial role in the metabolic activation by CYP3A4. The present study suggested that metabolic activation by CYP3A4 was one of the mechanisms of liver injury by nitrobenzodiazepines.

  1. Metabolically active microbial communities in uranium-contaminated subsurface sediments.

    PubMed

    Akob, Denise M; Mills, Heath J; Kostka, Joel E

    2007-01-01

    In order to develop effective bioremediation strategies for radionuclide contaminants, the composition and metabolic potential of microbial communities need to be better understood, especially in highly contaminated subsurface sediments for which little cultivation-independent information is available. In this study, we characterized metabolically active and total microbial communities associated with uranium-contaminated subsurface sediments along geochemical gradients. DNA and RNA were extracted and amplified from four sediment-depth intervals representing moderately acidic (pH 3.7) to near-neutral (pH 6.7) conditions. Phylotypes related to Proteobacteria (Alpha-, Beta-, Delta- and Gammaproteobacteria), Bacteroidetes, Actinobacteria, Firmicutes and Planctomycetes were detected in DNA- and RNA-derived clone libraries. Diversity and numerical dominance of phylotypes were observed to correspond to changes in sediment geochemistry and rates of microbial activity, suggesting that geochemical conditions have selected for well-adapted taxa. Sequences closely related to nitrate-reducing bacteria represented 28% and 43% of clones from the total and metabolically active fractions of the microbial community, respectively. This study provides the first detailed analysis of total and metabolically active microbial communities in radionuclide-contaminated subsurface sediments. Our microbial community analysis, in conjunction with rates of microbial activity, points to several groups of nitrate-reducers that appear to be well adapted to environmental conditions common to radionuclide-contaminated sites.

  2. Physical activity for the prevention and treatment of metabolic disorders.

    PubMed

    Montesi, Luca; Moscatiello, Simona; Malavolti, Marcella; Marzocchi, Rebecca; Marchesini, Giulio

    2013-12-01

    Metabolic syndrome and its various features (obesity, hypertension, dyslipidemia, diabetes, and nonalcoholic fatty liver disease) are increasing worldwide and constitute a severe risk for the sustainability of the present universal Italian health care system. Lifestyle interventions should be the first therapeutic strategy to prevent/treat metabolic diseases, far before pharmacologic treatment. The role of diet and weight loss has been fully ascertained, whereas the role of physical activity is frequently overlooked both by physicians and by patients. Physical activity has favorable effects on all components of the metabolic syndrome and on the resulting cardiovascular risk, the cornerstone in the development of cardiometabolic diseases. The quantity and the frequency of physical activity necessary to produce beneficial effects has not been defined as yet, but brisk walking is considered particularly appropriate, as it can be practiced by a large number of individuals, without any additional cost, and has a low rate of injury. The effects of exercise and leisure time physical activity extend from prevention to treatment of the various components of the metabolic syndrome, as well as to mood and quality of life. Any effort should be done to favor adherence to protocols of physical activity in the community.

  3. Molecular Evidence for Metabolically Active Bacteria in the Atmosphere

    PubMed Central

    Klein, Ann M.; Bohannan, Brendan J. M.; Jaffe, Daniel A.; Levin, David A.; Green, Jessica L.

    2016-01-01

    Bacterial metabolisms are responsible for critical chemical transformations in nearly all environments, including oceans, freshwater, and soil. Despite the ubiquity of bacteria in the atmosphere, little is known about the metabolic functioning of atmospheric bacterial communities. To gain a better understanding of the metabolism of bacterial communities in the atmosphere, we used a combined empirical and model-based approach to investigate the structure and composition of potentially active bacterial communities in air sampled at a high elevation research station. We found that the composition of the putatively active bacterial community (assayed via rRNA) differed significantly from the total bacterial community (assayed via rDNA). Rare taxa in the total (rDNA) community were disproportionately active relative to abundant taxa, and members of the order Rhodospirillales had the highest potential for activity. We developed theory to explore the effects of random sampling from the rRNA and rDNA communities on observed differences between the communities. We found that random sampling, particularly in cases where active taxa are rare in the rDNA community, will give rise to observed differences in community composition including the occurrence of “phantom taxa”, taxa which are detected in the rRNA community but not the rDNA community. We show that the use of comparative rRNA/rDNA techniques can reveal the structure and composition of the metabolically active portion of bacterial communities. Our observations suggest that metabolically active bacteria exist in the atmosphere and that these communities may be involved in the cycling of organic compounds in the atmosphere. PMID:27252689

  4. Association of Active and Sedentary Behaviors with Postmenopausal Estrogen Metabolism

    PubMed Central

    Dallal, Cher M.; Brinton, Louise A.; Matthews, Charles E.; Pfeiffer, Ruth M.; Hartman, Terryl J.; Lissowska, Jolanta; Falk, Roni T.; Garcia-Closas, Montserrat; Xu, Xia; Veenstra, Timothy D.; Gierach, Gretchen L.

    2015-01-01

    Purpose Physical activity may reduce endogenous estrogens but few studies have assessed effects on estrogen metabolism and none have evaluated sedentary behavior in relation to estrogen metabolism. We assessed relationships between accelerometer-measured physical activity and sedentary behavior and 15 urinary estrogens and estrogen metabolites (EM) among postmenopausal controls from a population-based breast cancer case-control study conducted in Poland (2000-2003). Methods Postmenopausal women (N=542) were ages 40 to 72 years and not currently using hormone therapy. Accelerometers, worn for seven days, were used to derive measures of average activity (counts/day) and sedentary behavior (<100 counts/min/day). EM were measured in 12-hour urine samples using liquid chromatography-tandem mass spectrometry. EM were analyzed individually, in metabolic pathways (C-2, -4, or -16), and as ratios relative to parent estrogens. Geometric means of EM by tertiles of accelerometer-measures, adjusted for age and body mass, were computed using linear models. Results High activity was associated with lower levels of estrone and estradiol (p-trend=0.01) while increased sedentary time was positively associated with these parent estrogens (p-trend=0.04). Inverse associations were observed between high activity and 2-methoxyestradiol, 4-methoxyestradiol, 17-epiestriol and 16-epiestriol (p-trend=0.03). Sedentary time was positively associated with methylated catechols in the 2- and 4-hydroxylation pathways (p-trend≤0.04). Women in the highest tertile of activity had increased hydroxylation at the C-2, -4, and -16 sites relative to parent estrogens (p-trend≤0.02) while increased sedentary time was associated with a lower 16-pathway:parent estrogen ratio (p-trend=0.01). Conclusions Higher activity was associated with lower urinary estrogens, possibly through increased estrogen hydroxylation and subsequent metabolism, while sedentary behavior may reduce metabolism. PMID:26460631

  5. Isomaltulose is actively metabolized in plant cells.

    PubMed

    Wu, Luguang; Birch, Robert G

    2011-12-01

    Isomaltulose is a structural isomer of sucrose (Suc). It has been widely used as a nonmetabolized sugar in physiological studies aimed at better understanding the regulatory roles and transport of sugars in plants. It is increasingly used as a nutritional human food, with some beneficial properties including low glycemic index and acariogenicity. Cloning of genes for Suc isomerases opened the way for direct commercial production in plants. The understanding that plants lack catabolic capabilities for isomaltulose indicated a possibility of enhanced yields relative to Suc. However, this understanding was based primarily on the treatment of intact cells with exogenous isomaltulose. Here, we show that sugarcane (Saccharum interspecific hybrids), like other tested plants, does not readily import or catabolize extracellular isomaltulose. However, among intracellular enzymes, cytosolic Suc synthase (in the breakage direction) and vacuolar soluble acid invertase (SAI) substantially catabolize isomaltulose. From kinetic studies, the specificity constant of SAI for isomaltulose is about 10% of that for Suc. Activity varied against other Suc isomers, with V(max) for leucrose about 6-fold that for Suc. SAI activities from other plant species varied substantially in substrate specificity against Suc and its isomers. Therefore, in physiological studies, the blanket notion of Suc isomers including isomaltulose as nonmetabolized sugars must be discarded. For example, lysis of a few cells may result in the substantial hydrolysis of exogenous isomaltulose, with profound downstream signal effects. In plant biotechnology, different V(max) and V(max)/K(m) ratios for Suc isomers may yet be exploited, in combination with appropriate developmental expression and compartmentation, for enhanced sugar yields.

  6. AMP-activated protein kinase and metabolic control

    PubMed Central

    Viollet, Benoit; Andreelli, Fabrizio

    2011-01-01

    AMP-activated protein kinase (AMPK), a phylogenetically conserved serine/threonine protein kinase, is a major regulator of cellular and whole-body energy homeostasis that coordinates metabolic pathways in order to balance nutrient supply with energy demand. It is now recognized that pharmacological activation of AMPK improves blood glucose homeostasis, lipid profile and blood pressure in insulin-resistant rodents. Indeed, AMPK activation mimics the beneficial effects of physical activity or those of calorie restriction by acting on multiple cellular targets. In addition it is now demonstrated that AMPK is one of the probable (albeit indirect) targets of major antidiabetic drugs including, the biguanides (metformin) and thiazolidinediones, as well as of insulin sensitizing adipokines (e.g., adiponectin). Taken together, such findings highlight the logic underlying the concept of targeting the AMPK pathway for the treatment of metabolic syndrome and type 2 diabetes. PMID:21484577

  7. ArthropodaCyc: a CycADS powered collection of BioCyc databases to analyse and compare metabolism of arthropods.

    PubMed

    Baa-Puyoulet, Patrice; Parisot, Nicolas; Febvay, Gérard; Huerta-Cepas, Jaime; Vellozo, Augusto F; Gabaldón, Toni; Calevro, Federica; Charles, Hubert; Colella, Stefano

    2016-01-01

    Arthropods interact with humans at different levels with highly beneficial roles (e.g. as pollinators), as well as with a negative impact for example as vectors of human or animal diseases, or as agricultural pests. Several arthropod genomes are available at present and many others will be sequenced in the near future in the context of the i5K initiative, offering opportunities for reconstructing, modelling and comparing their metabolic networks. In-depth analysis of these genomic data through metabolism reconstruction is expected to contribute to a better understanding of the biology of arthropods, thereby allowing the development of new strategies to control harmful species. In this context, we present here ArthropodaCyc, a dedicated BioCyc collection of databases using the Cyc annotation database system (CycADS), allowing researchers to perform reliable metabolism comparisons of fully sequenced arthropods genomes. Since the annotation quality is a key factor when performing such global genome comparisons, all proteins from the genomes included in the ArthropodaCyc database were re-annotated using several annotation tools and orthology information. All functional/domain annotation results and their sources were integrated in the databases for user access. Currently, ArthropodaCyc offers a centralized repository of metabolic pathways, protein sequence domains, Gene Ontology annotations as well as evolutionary information for 28 arthropod species. Such database collection allows metabolism analysis both with integrated tools and through extraction of data in formats suitable for systems biology studies.Database URL: http://arthropodacyc.cycadsys.org/.

  8. Biogeography of Metabolically Active Microbial Populations within the Subseafloor Biosphere

    NASA Astrophysics Data System (ADS)

    Reese, B. K.; Shepard, A.; St. Peter, C.; Mills, H. J.

    2011-12-01

    Microbial life in deep marine sediments is widespread, metabolically active and diverse. Evidence of prokaryotic communities in sediments as deep as 800 m below the seafloor (mbsf) have been found. By recycling carbon and nutrients through biological and geochemical processes, the deep subsurface has the potential to remain metabolically active over geologic time scales. While a vast majority of the subsurface biosphere remains under studied, recent advances in molecular techniques and an increased focus on microbiological sampling during IODP expeditions have provided the initial steps toward better characterizations of the microbial communities. Coupling of geochemistry and RNA-based molecular analysis is essential to the description of the active microbial populations within the subsurface biosphere. Studies based on DNA may describe the taxa and metabolic pathways from the total microbial community within the sediment, whether the cells sampled were metabolically active, quiescent or dead. Due to a short lifespan within a cell, only an RNA-based analysis can be used to identify linkages between active populations and observed geochemistry. This study will coalesce and compare RNA sequence and geochemical data from Expeditions 316 (Nankai Trough), 320 (Pacific Equatorial Age Transect), 325 (Great Barrier Reef) and 329 (South Pacific Gyre) to evaluate the biogeography of microbial lineages actively altering the deep subsurface. The grouping of sediments allows for a wide range of geochemical environments to be compared, including two environments limited in organic carbon. Significant to this study is the use of similar extraction, amplification and simultaneous 454 pyrosequencing on all sediment populations allowing for robust comparisons with similar protocol strengths and biases. Initial trends support previously described reduction of diversity with increasing depth. The co-localization of active reductive and oxidative lineages suggests a potential cryptic

  9. Biochemical studies on the metabolic activation of halogenated alkanes.

    PubMed Central

    Cheeseman, K H; Albano, E F; Tomasi, A; Slater, T F

    1985-01-01

    This paper reviews recent investigations by Slater and colleagues into the metabolic activation of halogenated alkanes in general and carbon tetrachloride in particular. It is becoming increasingly accepted that free radical intermediates are involved in the toxicity of many such compounds through mechanisms including lipid peroxidation, covalent binding, and cofactor depletion. Here we describe the experimental approaches that are used to establish that halogenated alkanes are metabolized in animal tissues to reactive free radicals. Electron spin resonance spectroscopy is used to identify free-radical products, often using spin-trapping compounds. The generation of specific free radicals by radiolytic methods is useful in the determination of the precise reactivity of radical intermediates postulated to be injurious to the cell. The enzymic mechanism of the production of such free radicals and their subsequent reactions with biological molecules is studied with specific metabolic inhibitors and free-radical scavengers. These combined techniques provide considerable insight into the process of metabolic activation of halogenated compounds. It is readily apparent, for instance, that the local oxygen concentration at the site of activation is of crucial importance to the subsequent reactions; the formation of peroxy radical derivatives from the primary free-radical product is shown to be of great significance in relation to carbon tetrachloride and may be of general importance. However, while these studies have provided much information on the biochemical mechanisms of halogenated alkane toxicity, it is clear that many problems remain to be solved. PMID:3007102

  10. Enumerating Minimal Active Metabolic Pathways by Model Generation

    NASA Astrophysics Data System (ADS)

    Soh, Takehide; Inoue, Katsumi

    In systems biology, identifying vital functions like glycolysis from a given metabolic pathway is important to understand living organisms. In this paper, we particularly focus on the problem of enumerating minimal active pathways producing target metabolites from source metabolites. We represent the problem in propositional formulas and solve it through minimal model generation. An advantage of our method is that each solution satisfies qualitative laws of biochemical reactions. Moreover, we can calculate such solutions for a cellular scale metabolic pathway within a few seconds. In experiments, we have applied our method to a whole Escherichia coli metabolic pathway. As a result, we found a minimal set of reactions corresponding to the conventional glycolysis pathway described in a biological database EcoCyc.

  11. CATALASE ACTIVITY OF TWO STREPTOCOCCUS FAECALIS STRAINS AND ITS ENHANCEMENT BY AEROBIOSIS AND ADDED CATIONS1

    PubMed Central

    Jones, Dorothy; Deibel, R. H.; Niven, C. F.

    1964-01-01

    Jones, Dorothy (American Meat Institute Foundation, Chicago, Ill.), R. H. Deibel, and C. F. Niven, Jr. Catalase activity of two Streptococcus faecalis strains and its enhancement by aerobiosis and added cations. J. Bacteriol. 88:602–610. 1964.—The nature of catalase activity noted in two unusual Streptococcus faecalis strains was determined. Enzyme activity was lost slowly when cultures were maintained by daily transfer in test tubes of broth media. Loss of activity could be prevented by aerobic culture. Supplementation of the growth medium with ferric, manganese, and zinc ions, as well as aerobiosis, enhanced catalase activity. However, addition of these cations to cell suspensions or to cell-free extracts did not increase catalase activity. Although oxygen was observed to be one of the reaction end products, the catalase activity was not inhibited by cyanide or azide, and the iron-porphyrin coenzyme of classical catalase was not detected. The enzyme was purified 185-fold by precipitation with ammonium sulfate, followed by chromotography on a diethylaminoethyl cellulose column. PMID:14208495

  12. Heightened hurricane activity on the Little Bahama Bank from 1350 to 1650 AD

    NASA Astrophysics Data System (ADS)

    van Hengstum, Peter J.; Donnelly, Jeffrey P.; Toomey, Michael R.; Albury, Nancy A.; Lane, Philip; Kakuk, Brian

    2014-09-01

    Deciphering how the climate system has controlled North Atlantic tropical cyclone activity through the Holocene will require a larger observational network of prehistoric hurricane activity. Problematically, the tropical North Atlantic is dominated by carbonate landscapes that typically preserve poorer quality coastal sediment records in comparison to their temperate-region counterparts (e.g., sedimentation continuity and rate). Coastal karst basins (CKBs), such as sinkholes, blueholes, and underwater caves, are widely distributed on carbonate platforms and contain overlooked sedimentary records. Here we present a millennium of hurricane deposits on the Little Bahama Bank archived in a 165 cm core that was extracted from 69 m below sea level in a bluehole on Great Abaco Island, The Bahamas. The coarse-grained overwash deposits associated with both hurricanes Jeanne (2004) and Floyd (1999) were identified using radioisotopes (137Cs, 14C, 210Pb), and indicate that the bluehole is sensitive to hurricane-induced sedimentation. Over the last millennium, the Little Bahama Bank experienced heightened hurricane activity from 1350 to 1650 AD. The simplest explanation for this active interval is that favorable climate conditions (El Niño, West African Monsoon, and sea surface temperatures) encouraged North Atlantic hurricane activity at that time. However, asynchronous hurricane activity at similar latitudes in the North Atlantic and Gulf of Mexico suggest that regional oceanography has modulated or amplified regional hurricane activity over the last millennium.

  13. Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis

    PubMed Central

    Rynes, Jan; Donohoe, Colin D.; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek

    2012-01-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins. PMID:22851689

  14. Metabolic activation of 2-methylfuran by rat microsomal systems

    SciTech Connect

    Ravindranath, V.; Boyd, M.R.

    1985-05-01

    2-Methylfuran (2-MF), a constituent of cigarette smoke and coffee, causes necrosis of liver, lungs, and kidneys in rodents. 2-MF is metabolically activated by mixed-function oxidases to acetylacrolein, a reactive metabolite that binds covalently to microsomal protein. The hepatic microsomal metabolism of 2-MF to reactive metabolite required the presence of NADPH and oxygen and was dependent on incubation time and substrate concentration. The microsomal metabolism of 2-MF was inducible by pretreatment of rats with phenobarbital and was inhibited by piperonyl butoxide and N-octyl imidazole, which indicates that the metabolism of 2-MF may be mediated by cytochrome P-450. Acetylacrolein was a potent inhibitor of mixed-function oxidase and completely inhibited the microsomal metabolism of 2-MF, indicating that 2-MF is a suicide substrate for the enzyme. The sulfhydryl nucleophile cysteine was a better trapping agent of the reactive metabolite of 2-MF than N-acetylcysteine or glutathione. Lysine decreased the covalent binding of 2-MF metabolites, presumably by reacting with the aldehyde group of acetylacrolein. In addition, in the presence of NADPH, 2-MF was bioactivated by both pulmonary and renal cortical microsomes to reactive metabolites that were covalently bound to microsomal proteins.

  15. Dynamic model for selective metabolic activation in chemical carcinogenesis

    SciTech Connect

    Selkirk, J.K.; MacLeod, M.C.

    1980-01-01

    Theoretical calculations predict the relative ease of formation of carbonium ions from 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene-9,10-oxide or from either of the 2 symmetrical bay regions of B(e)P, and suggest their attraction to cellular nucleophiles. When both isomers were metabolized by hamster embryo fibroblasts (HEF) and the products analyzed, the results showed that the probable reason for benzo(e)pyrene's lack of carcinogenicity was its metabolic preference to attack the molecule away from the bay-region area. Particularly striking was the absence of any evidence for the formation of a significant amount of B(e)P-9,10-dihydrodiol. This suggests a metabolic basis for the relative lack of carcinogenic and mutagenic activity of B(e)P. The reason for this is not clear but may be due to physical or chemical factors such as membrane solubility or stereochemical requirements of the active site of the enzyme. The bay-region theory of PAH carcinogenesis predicts that carbonium ion formation from 9,10-dihydro-9,10-dihydroxybenzo(e)pyrene-11, 12-oxide, if formed, would be energetically favorable. Thus, the inability of HEF and microcomes to form B(e)P-9,10-dihydrodiol, the precursor of its potentially highly reactive diol-epoxide, would explain the relative inertness of B(e)P in several biological systems. As the subtle biochemical interactions of the various carcinogen intermediates become clarified, it becomes apparent that susceptibility and resistance to malignant transformation are based on a complex set of both chemical and physical parameters. It is becoming clear that metabolism kinetics, membrane interaction, and the role of nuclear metabolism help dictate the passage of the carcinogen and its reactive intermediates into and through the metabolic machinery of the cell. (ERB)

  16. Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease

    PubMed Central

    Azhar, Salman

    2011-01-01

    Metabolic syndrome (MetS) is a constellation of risk factors including insulin resistance, central obesity, dyslipidemia and hypertension that markedly increase the risk of Type 2 diabetes (T2DM) and cardiovascular disease (CVD). The peroxisome proliferators-activated receptor (PPAR) isotypes, PPARα, PPARδ/β and PPARγ are ligand-activated nuclear transcription factors, which modulate the expression of an array of genes that play a central role in regulating glucose, lipid and cholesterol metabolism, where imbalance can lead to obesity, T2DM and CVD. They are also drug targets, and currently, PPARα (fibrates) and PPARγ (thiazolodinediones) agonists are in clinical use for treating dyslipidemia and T2DM, respectively. These metabolic characteristics of the PPARs, coupled with their involvement in metabolic diseases, mean extensive efforts are underway worldwide to develop new and efficacious PPAR-based therapies for the treatment of additional maladies associated with the MetS. This article presents an overview of the functional characteristics of three PPAR isotypes, discusses recent advances in our understanding of the diverse biological actions of PPARs, particularly in the vascular system, and summarizes the developmental status of new single, dual, pan (multiple) and partial PPAR agonists for the clinical management of key components of MetS, T2DM and CVD. It also summarizes the clinical outcomes from various clinical trials aimed at evaluating the atheroprotective actions of currently used fibrates and thiazolodinediones. PMID:20932114

  17. Sampling and major element chemistry of the recent (A.D. 1631-1944) Vesuvius activity

    USGS Publications Warehouse

    Belkin, H.E.; Kilburn, C.R.J.; de Vivo, B.

    1993-01-01

    Detailed sampling of the Vesuvius lavas erupted in the period A.D. 1631-1944 provides a suite of samples for comprehensive chemical analyses and related studies. Major elements (Si, Ti, Al, Fetotal, Mn, Mg, Ca, Na, K and P), volatile species (Cl, F, S, H2O+, H2O- and CO2), and ferrous iron (Fe2+) were determined for one hundred and forty-nine lavas and five tephra from the A.D. 1631-1944 Vesuvius activity. The lavas represent a relatively homogeneous suite with respect to SiO2, TiO2, FeOtotal, MnO and P2O5, but show systematic variations among MgO, K2O, Na2O, Al2O3 and CaO. The average SiO2 content is 48.0 wt.% and the rocks are classified as tephriphonolites according to their content of alkalis. All of the lavas are silica-undersaturated and are nepheline, leucite, and olivine normative. There is no systematic variation in major-element composition with time, over the period A.D. 1631-1944. The inter-eruption and intra-eruption compositional differences are the same magnitude. The lavas are highly porphyritic with clinopyroxene and leucite as the major phases. Fractionation effects are not reflected in the silica content of the lavas. The variability of MgO, K2O, Na2O, and CaO can be modelled as a relative depletion or accumulation of clinopyroxene. ?? 1993.

  18. Revealing a strongly reddened, faint active galactic nucleus population by stacking deep co-added images

    NASA Astrophysics Data System (ADS)

    Varga, József; Csabai, István.; Dobos, László

    2012-10-01

    More than half of the sources identified by recent radio sky surveys have not been detected by wide-field optical surveys. We present a study, based on our co-added image stacking technique, in which our aim is to detect the optical emission from unresolved, isolated radio sources of the Very Large Array (VLA) Faint Images of the Radio Sky at Twenty-cm (FIRST) survey that have no identified optical counterparts in the Sloan Digital Sky Survey (SDSS) Stripe 82 co-added data set. From the FIRST catalogue, 2116 such radio point sources were selected, and cut-out images, centred on the FIRST coordinates, were generated from the Stripe 82 images. The already co-added cut-outs were stacked once again to obtain images of high signal-to-noise ratio, in the hope that optical emission from the radio sources would become detectable. Multiple stacks were generated, based on the radio luminosity of the point sources. The resulting stacked images show central peaks similar to point sources. The peaks have very red colours with steep optical spectral energy distributions. We have found that the optical spectral index αν falls in the range -2.9 ≤ αν ≤ -2.2 (Sν∝ναν), depending only weakly on the radio flux. The total integration times of the stacks are between 270 and 300 h, and the corresponding 5σ detection limit is estimated to be about mr ≃ 26.6 mag. We argue that the detected light is mainly from the central regions of dust-reddened Type 1 active galactic nuclei. Dust-reddened quasars might represent an early phase of quasar evolution, and thus they can also give us an insight into the formation of massive galaxies. The data used in the paper are available on-line at http://www.vo.elte.hu/doublestacking.

  19. Metabolic activity of bacterial cell enumerated by direct viable count. [Escherichia coli; Salmonella enteritidis

    SciTech Connect

    Roszak, D.B.; Colwell, R.R.

    1987-12-01

    The direct viable count (DVC) method was modified by incorporation radiolabeled substrates in microautoradiographic analyses to assess bacterial survival in controlled laboratory microcosms. The DVC method, which permits enumeration of culturable and nonculturable cells, discriminates those cells that are responsive to added nutrients but in which division is inhibited by the addition of nalidixic acid. The resulting elongated cells represent all viable cells; this includes those that are culturable on routine media and those that are not. Escherichia coli and Salmonella enteritidis were employed in the microcosm studies, and radiolabeled substrates included (methyl-/sup 3/H) thymidine or (U-/sup 14/C) glutamic acid. Samples taken at selected intervals during the survival experiments were examined by epifluorescence microscopy to enumerate cells by the DVC and acridine orange direct count methods, as well as by culture methods. Good correlation was obtained for cell-associated metabolic activity, measured by microautoradiography and substrate responsiveness (by the DVC method) at various stages of survival. Of the cells responsive to nutrients by the DVC method, ca. 90% were metabolically active by the microautoradiographic method. No significant difference was observed between DVC enumerations with or without added radiolabeled substrate.

  20. Activity of anandamide (AEA) metabolic enzymes in rat placental bed.

    PubMed

    Fonseca, B M; Battista, N; Correia-da-Silva, G; Rapino, C; Maccarrone, M; Teixeira, N A

    2014-11-01

    Endocannabinoids are endogenous lipid mediators, with anandamide (AEA) being the first member identified. It is now widely accepted that AEA influences early pregnancy events and its levels, which primarily depend on its synthesis by an N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and degradation by a fatty acid amide hydrolase (FAAH), must be tightly regulated. Previous studies demonstrated that AEA levels require in situ regulation of these respective metabolic enzymes, and thus, any disturbance in AEA levels may impact maternal remodeling processes occurring during placental development. In this study, the activities of the AEA-metabolic enzymes that result in the establishment of proper local AEA levels during rat gestation were examined. Here, we demonstrate that during placentation NAPE-PLD and FAAH activities change in a temporal manner. Our findings suggest that NAPE-PLD and FAAH create the appropriate AEA levels required for tissue remodeling in the placental bed, a process essential to pregnancy maintenance.

  1. Measurement of Metabolic Activity in Dormant Spores of Bacillus Species

    DTIC Science & Technology

    2015-01-14

    SECURITY CLASSIFICATION OF: Spores of Bacillus megaterium and Bacillus subtilis were harvested shortly after release from sporangia, incubated under...Dec-2014 Approved for Public Release; Distribution Unlimited Final Report: Measurement of Metabolic Activity in Dormant Spores of Bacillus Species...Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 spores, Bacillus , spore dormancy, 3-phosphoglycerate REPORT DOCUMENTATION PAGE 11

  2. Haloacetonitriles: metabolism, genotoxicity, and tumor-initiating activity

    SciTech Connect

    Lin, E.L.C.; Daniel, F.B.; Herren-Freund, S.L.; Pereira, M.A.

    1986-11-01

    Haloacetonitriles (HAN) are drinking water contaminants produced during chlorine disinfection. This paper evaluates metabolism, genotoxicity, and tumor-initiating activity of these chemicals. The alkylating potential of the HAN to react with the electrophile-trapping agent, 4-(p-nitrobenzyl)pyridine, followed the order dibromoacetonitrile (DBAN) > bromochloroacetonitrile (BCAN) > chloroacetonitrile (CAN) > dichloroacetonitrile (DCAN) > trichloroacetonitrile (TCAN). When administered orally to rats, the HAN were metabolized to cyanide and excreted in the urine as thiocyanate. The extent of thiocyanate excretion was CAN > BCAN > DCAN > DDAN >> TCAN. Haloacetonitriles inhibited in vitro microsomal dimethylnitrosamine demethylase (DMN-DM) activity. The most potent inhibitors were DBAN and BCAN. The HAN produced DNA strand breaks in cultured human lymphoblastic (CCRF-CEM) cells. TCAN was the most potent DNA strand breaker. DCAN reacted with polyadenylic acid and DNA to form adducts in a cell-free system. None of the HAN initiated ..gamma..-glutamyltranspeptidase (GGT) foci when assayed for tumor-initiating activity in rat liver foci bioassay. In summary, the HAN were demonstrated to possess alkylating activity and genotoxicity in vitro and appeared after oral administration to possess biological activity as indicated by the inhibition of DMN-DM by TCAN but appeared to lack genotoxic and tumor-initiating activity in rat liver. It is proposed that if the HAN found in drinking water pose a carcinogenic hazard it would be limited to the gastrointestinal tract.

  3. Activity syndromes and metabolism in giant deep-sea isopods

    NASA Astrophysics Data System (ADS)

    Wilson, Alexander D. M.; Szekeres, Petra; Violich, Mackellar; Gutowsky, Lee F. G.; Eliason, Erika J.; Cooke, Steven J.

    2017-03-01

    Despite growing interest, the behavioural ecology of deep-sea organisms is largely unknown. Much of this scarcity in knowledge can be attributed to deepwater animals being secretive or comparatively 'rare', as well as technical difficulties associated with accessing such remote habitats. Here we tested whether two species of giant marine isopod (Bathynomus giganteus, Booralana tricarinata) captured from 653 to 875 m in the Caribbean Sea near Eleuthera, The Bahamas, exhibited an activity behavioural syndrome across two environmental contexts (presence/absence of food stimulus) and further whether this syndrome carried over consistently between sexes. We also measured routine metabolic rate and oxygen consumption in response to a food stimulus in B. giganteus to assess whether these variables are related to individual differences in personality. We found that both species show an activity syndrome across environmental contexts, but the underlying mechanistic basis of this syndrome, particularly in B. giganteus, is unclear. Contrary to our initial predictions, neither B. giganteus nor B. tricarinata showed any differences between mean expression of behavioural traits between sexes. Both sexes of B. tricarinata showed strong evidence of an activity syndrome underlying movement and foraging ecology, whereas only male B. giganteus showed evidence of an activity syndrome. Generally, individuals that were more active and bolder, in a standard open arena test were also more active when a food stimulus was present. Interestingly, individual differences in metabolism were not related to individual differences in behaviour based on present data. Our study provides the first measurements of behavioural syndromes and metabolism in giant deep-sea isopods.

  4. Metabolism of mometasone furoate and biological activity of the metabolites.

    PubMed

    Sahasranaman, S; Issar, M; Hochhaus, G

    2006-02-01

    To better evaluate the pharmacokinetic and pharmacodynamic properties of the new inhaled glucocorticoid mometasone furoate (MF), the metabolism of MF was evaluated in rat and human tissues and in rat after i.v. administration. Metabolic studies with 3H-MF in human and rat plasma and S9 fractions of human and rat lung showed relatively high stability and a degradation pattern similar to that seen in buffer systems. MF was efficiently metabolized into at least five metabolites in S9 fractions of both rat and human liver. There were, however, quantitative differences in the metabolites between the two species. The apparent half-life of MF in the S9 fraction of human liver was found to be 3 times greater compared with that in rat. MET1, the most polar metabolite, was the major metabolite in rat liver fractions, whereas both MET1 and MET2 were formed to an equal extent in human liver. Metabolism and distribution studies in rats after intravenous and intratracheal administration of [1,2-(3)H]MF revealed that most of the radioactivity (approximately 90%) was present in the stomach, intestines, and intestinal contents, suggesting biliary excretion of MF and its metabolites. Radiochromatography showed that most radioactivity was associated with MET1, MET2, and MET 3. Fractionation of the high-performance liquid chromatography eluate (MET1-5) revealed that only MF [relative binding affinity (RBA) 2900] and MET2 (RBA 700) had appreciable glucocorticoid receptor binding affinity. These results suggest that MF undergoes distinct extrahepatic metabolism but generates active metabolites that might be in part responsible for the systemic side effects of MF.

  5. Changes to coral health and metabolic activity under oxygen deprivation

    PubMed Central

    Richmond, Robert H.

    2016-01-01

    On Hawaiian reefs, the fast-growing, invasive algae Gracilaria salicornia overgrows coral heads, restricting water flow and light, thereby smothering corals. Field data shows hypoxic conditions (dissolved oxygen (DO2) < 2 mg/L) occurring underneath algal mats at night, and concurrent bleaching and partial tissue loss of shaded corals. To analyze the impact of nighttime oxygen-deprivation on coral health, this study evaluated changes in coral metabolism through the exposure of corals to chronic hypoxic conditions and subsequent analyses of lactate, octopine, alanopine, and strombine dehydrogenase activities, critical enzymes employed through anaerobic respiration. Following treatments, lactate and octopine dehydrogenase activities were found to have no significant response in activities with treatment and time. However, corals subjected to chronic nighttime hypoxia were found to exhibit significant increases in alanopine dehydrogenase activity after three days of exposure and strombine dehydrogenase activity starting after one overnight exposure cycle. These findings provide new insights into coral metabolic shifts in extremely low-oxygen environments and point to ADH and SDH assays as tools for quantifying the impact of hypoxia on coral health. PMID:27114888

  6. Metabolic, anabolic, and mitogenic insulin responses: A tissue-specific perspective for insulin receptor activators

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insulin acts as the major regulator of the fasting-to-fed metabolic transition by altering substrate metabolism, promoting energy storage, and helping activate protein synthesis. In addition to its glucoregulatory and other metabolic properties, insulin can also act as a growth factor. The metabolic...

  7. Hepatic metabolism of glucose and linoleic acid varies in relation to susceptibility to fatty liver in ad libitum-fed Muscovy and Pekin ducks.

    PubMed

    Saez, Gladys; Baéza, Elisabeth; Davail, Stéphane; Durand, Denys; Bauchart, Dominique; Gruffat, Dominique

    2009-02-01

    The susceptibility to develop hepatic steatosis is known to differ between duck species, especially between Muscovy and Pekin ducks. This difference could be explained by either differential responses of species to overfeeding or genetic differences in hepatic lipid metabolism. The aim of the present study was to compare the intensities of the different hepatic pathways (oxidation, lipogenesis, esterification, secretion, etc.) of the two main nutrients (glucose and linoleic acid (LA)) reaching the liver of ad libitum-fed Muscovy (n 6) and Pekin (n 6) ducks using the ex vivo method of liver slices incubated for 16 h with [U-14C]glucose, [1-14C]LA and [35S]methionine added to the survival medium. In such experimental conditions, the lipogenesis pathway from glucose was 2-fold higher (P<0.05) in the liver of the Muscovy duck than in that of the Pekin duck. Furthermore, the hepatic uptake of LA was 2-fold higher (P<0.05) in the Muscovy duck than in the Pekin duck leading to a 2-fold higher (P<0.05) esterification of this fatty acid in the liver of the Muscovy duck. The hepatic secretion of VLDL was higher (P<0.01) in the Muscovy duck than in the Pekin duck but insufficient to prevent lipid accumulation in the liver of the Muscovy duck. In conclusion, these results show the influence of the species on the hepatic metabolism of ducks in relation to their susceptibility to develop fatty liver. These results should shed light on the metabolic regulations that might underlie susceptibility to hepatic steatosis in the the human liver.

  8. Metabolic activity of subseafloor microbes in the South Pacific Gyre

    NASA Astrophysics Data System (ADS)

    Morono, Y.; Ito, M.; Terada, T.; Inagaki, F.

    2013-12-01

    The South Pacific Gyre (SPG) is characterized as the most oligotrophic open ocean environment. The sediment is rich in oxygen but poor in energy-sources such as reduced organic matter, and hence harbors very low numbers of microbial cells in relatively shallow subseafloor sediment (D'Hondt et al., 2009; Kallmeyer et al., 2012). In such an energy-limited sedimentary habitat, a small size of microbial community persists living functions with extraordinary low oxygen-consumption rate (Røy et al., 2012). During IODP Expedition 329, a series of sediment samples were successfully recovered from 7 drill sites (U1365-1371) from the seafloor to basement in the SPG, providing an unprecedented opportunity to study metabolic activity of the aerobic subseafloor microbial communities. We initiated incubation onboard by adding stable isotope-labeled substrates to the freshly collected sediment sample, such as 13C and/or 15N-labeled bicarbonate, glucose, amino acids, acetate, and ammonium under the (micro-) aerobic condition. One of the technological challenges in this study is to harvest microbial cells from very low-biomass sediment samples for the analysis using nano-scale secondary ion mass spectrometry (NanoSIMS). To address the technical issue, we improved existing cell separation technique for the SPG sediment samples with small inorganic zeolitic grains. By monitoring cell recovery rates through an image-based cell enumeration technique (Morono et al., 2009), we found that cell recovery rates in the SPG sediment samples are generally lower than those in other oceanographic settings (i.e., organic-rich ocean margin sediments). To gain higher cell recovery ratio, we applied multiple density gradient layers, resulting in the cell recovery ratio up to around 80-95% (Morono et al., in press). Then, using the newly developed cell separation technique, we successfully sorted enough number of microbial cells in small spots on the membrane (i.e., 103 to 105 cells per spot). Nano

  9. Antifungal activity by vapor contact of essential oils added to amaranth, chitosan, or starch edible films.

    PubMed

    Avila-Sosa, Raúl; Palou, Enrique; Jiménez Munguía, María Teresa; Nevárez-Moorillón, Guadalupe Virginia; Navarro Cruz, Addí Rhode; López-Malo, Aurelio

    2012-02-01

    Antimicrobial agents can be incorporated into edible films to provide microbiological stability, since films can be used as carriers of a variety of additives to extend product shelf life and reduce the risk of microbial growth on food surfaces. Addition of antimicrobial agents to edible films offers advantages such as the use of small antimicrobial concentrations and low diffusion rates. The aim of this study was to evaluate inhibition by vapor contact of Aspergillus niger and Penicillium digitatum by selected concentrations of Mexican oregano (Lippia berlandieri Schauer), cinnamon (Cinnamomum verum) or lemongrass (Cymbopogon citratus) essential oils (EOs) added to amaranth, chitosan, or starch edible films. Essential oils were characterized by gas chromatography-mass spectrometry (GC/MS) analysis. Amaranth, chitosan and starch edible films were formulated with essential oil concentrations of 0.00, 0.25, 0.50, 0.75, 1.00, 2.00, or 4.00%. Antifungal activity was evaluated by determining the mold radial growth on agar media inoculated with A. niger and P. digitatum after exposure to vapors arising from essential oils added to amaranth, chitosan or starch films using the inverted lid technique. The modified Gompertz model adequately described mold growth curves (mean coefficient of determination 0.991 ± 0.05). Chitosan films exhibited better antifungal effectiveness (inhibition of A. niger with 0.25% of Mexican oregano and cinnamon EO; inhibition of P. digitatum with 0.50% EOs) than amaranth films (2.00 and 4.00% of cinnamon and Mexican oregano EO were needed to inhibit the studied molds, respectively). For chitosan and amaranth films a significant increase (p<0.05) of lag phase was observed among film concentrations while a significant decrease (p<0.05) of maximum specific growth was determined. Chitosan edible films incorporating Mexican oregano or cinnamon essential oil could improve the quality of foods by the action of the volatile compounds on surface growth

  10. Moonlighting transcriptional activation function of a fungal sulfur metabolism enzyme

    PubMed Central

    Levati, Elisabetta; Sartini, Sara; Bolchi, Angelo; Ottonello, Simone; Montanini, Barbara

    2016-01-01

    Moonlighting proteins, including metabolic enzymes acting as transcription factors (TF), are present in a variety of organisms but have not been described in higher fungi so far. In a previous genome-wide analysis of the TF repertoire of the plant-symbiotic fungus Tuber melanosporum, we identified various enzymes, including the sulfur-assimilation enzyme phosphoadenosine-phosphosulfate reductase (PAPS-red), as potential transcriptional activators. A functional analysis performed in the yeast Saccharomyces cerevisiae, now demonstrates that a specific variant of this enzyme, PAPS-red A, localizes to the nucleus and is capable of transcriptional activation. TF moonlighting, which is not present in the other enzyme variant (PAPS-red B) encoded by the T. melanosporum genome, relies on a transplantable C-terminal polypeptide containing an alternating hydrophobic/hydrophilic amino acid motif. A similar moonlighting activity was demonstrated for six additional proteins, suggesting that multitasking is a relatively frequent event. PAPS-red A is sulfur-state-responsive and highly expressed, especially in fruitbodies, and likely acts as a recruiter of transcription components involved in S-metabolism gene network activation. PAPS-red B, instead, is expressed at low levels and localizes to a highly methylated and silenced region of the genome, hinting at an evolutionary mechanism based on gene duplication, followed by epigenetic silencing of this non-moonlighting gene variant. PMID:27121330

  11. Metabolism

    MedlinePlus

    Metabolism refers to all the physical and chemical processes in the body that convert or use energy, ... Tortora GJ, Derrickson BH. Metabolism. In: Tortora GJ, Derrickson ... Physiology . 14th ed. Hoboken, NJ: John Wiley & Sons; 2014:chap ...

  12. Metabolism

    MedlinePlus

    ... El metabolismo Metabolism Basics Our bodies get the energy they need from food through metabolism, the chemical ... that convert the fuel from food into the energy needed to do everything from moving to thinking ...

  13. Metabolic transistor strategy for controlling electron transfer chain activity in Escherichia coli.

    PubMed

    Wu, Hui; Tuli, Leepika; Bennett, George N; San, Ka-Yiu

    2015-03-01

    A novel strategy to finely control a large metabolic flux by using a "metabolic transistor" approach was established. In this approach a small change in the level or availability of an essential component for the process is controlled by adding a competitive reaction that affects a precursor or an intermediate in its biosynthetic pathway. The change of the basal level of the essential component, considered as a base current in a transistor, has a large effect on the flux through the major pathway. In this way, the fine-tuning of a large flux can be accomplished. The "metabolic transistor" strategy was applied to control electron transfer chain function by manipulation of the quinone synthesis pathway in Escherichia coli. The achievement of a theoretical yield of lactate production under aerobic conditions via this strategy upon manipulation of the biosynthetic pathway of the key participant, ubiquinone-8 (Q8), in an E. coli strain provides an in vivo, genetically tunable means to control the activity of the electron transfer chain and manipulate the production of reduced products while limiting consumption of oxygen to a defined amount.

  14. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.

    PubMed

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin.

  15. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells

    PubMed Central

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin. PMID:27348124

  16. In vivo enzyme activity in inborn errors of metabolism

    SciTech Connect

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D. )

    1990-08-01

    Low-dose continuous infusions of (2H5)phenylalanine, (1-13C)propionate, and (1-13C)leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.

  17. Dietary electrolyte balance affects growth performance, amylase activity and metabolic response in the meagre (Argyrosomus regius).

    PubMed

    Magnoni, Leonardo J; Salas-Leiton, Emilio; Peixoto, Maria-João; Pereira, Luis; Silva-Brito, Francisca; Fontinha, Filipa; Gonçalves, José F M; Wilson, Jonathan M; Schrama, Johan W; Ozório, Rodrigo O A

    2017-03-16

    Dietary ion content is known to alter the acid-base balance in freshwater fish. The current study investigated the metabolic impact of acid-base disturbances produced by differences in dietary electrolyte balance (DEB) in the meagre (Argyrosomus regius), an euryhaline species. Changes in fish performance, gastric chyme characteristics, pH and ion concentrations in the bloodstream, digestive enzyme activities and metabolic rates were analyzed in meagre fed ad libitum two experimental diets (DEB 200 or DEB 700mEq/kg) differing in the Na2CO3 content for 69days. Fish fed the DEB 200 diet had 60-66% better growth performance than the DEB 700 group. Meagre consuming the DEB 200 diet were 90-96% more efficient than fish fed the DEB 700 diet at allocating energy from feed into somatic growth. The pH values in blood were significantly lower in the DEB 700 group 2h after feeding when compared to DEB 200, indicating that acid-base balance in meagre was affected by electrolyte balance in diet. Osmolality, and Na(+) and K(+) concentrations in plasma did not vary with the dietary treatment. Gastric chyme in the DEB 700 group had higher pH values, dry matter, protein and energy contents, but lower lipid content than in the DEB 200 group. Twenty-four hours after feeding, amylase activity was higher in the gastrointestinal tract of DEB 700 group when compared to the DEB 200 group. DEB 700 group had lower routine metabolic (RMR) and standard metabolic (SMR) rates, indicating a decrease in maintenance energy expenditure 48h after feeding the alkaline diet. The current study demonstrates that feeding meagre with an alkaline diet not only causes acid-base imbalance, but also negatively affects digestion and possibly nutrient assimilation, resulting in decreased growth performance.

  18. [Ultrastructure and metabolic activity of pea mitochondria under clinorotation].

    PubMed

    Brykov, V A; Generozova, I P; Shugaev, A G

    2012-01-01

    Experimental data on the mitochondrial ultrastructure and tissue respiration in root apex as well as metabolic activity of the organelles isolated from pea seedling roots after 5-day of clinorotation are presented. It was shown that mitochondrial condensation in the distal elongation zone correlated with an increased rate of oxygen uptake on 7%. We also observed increase in rate of malate oxidation and respiratory control ratio increased simultaneously with a decreased in efficiency of oxidative phosphorylation. Such character of mitochondrial rearrangements in simulated microgravity is assumed to be a consequence of adaptation to these conditions.

  19. Solar activity and climate change during the 1750 A.D. solar minimum

    NASA Astrophysics Data System (ADS)

    Bard, Edouard; Baroni, Mélanie; Aster Team

    2015-04-01

    The number of sunspots and other characteristics have been widely used to reconstruct the solar activity beyond the last three decades of accurate satellite measurements. It has also been possible to reconstruct the long-term solar behavior by measuring the abundance on Earth of cosmogenic nuclides such as carbon 14 and beryllium 10. These isotopes are formed by the interaction of galactic cosmic rays with atmospheric molecules. Accelerator mass spectrometry is used to measure the abundance of these isotopes in natural archives such as polar ice (for 10Be), tree rings and corals (for 14C). Over the last millennium, the solar activity has been dominated by alternating active and quiet periods, such as the Maunder Minimum, which occurred between 1645 and 1715 A.D. The climate forcing of this solar variability is the subject of intense research, both because the exact scaling in terms of irradiance is still a matter of debate and because other solar variations may have played a role in amplifying the climatic response. Indeed, the past few decades of accurate solar measurements do not include conditions equivalent to an extended solar minimum. A further difficulty of the analysis lies in the presence of other climate forcings during the last millennium, which are superimposed on the solar variations. Finally, the inherent precision of paleotemperature proxies are close to the signal amplitude retrieved from various paleoclimate archives covering the last millennium. Recent model-data comparisons for the last millennium have led to the conclusion that the solar forcing during this period was minor in comparison to volcanic eruptions and greenhouse gas concentrations (e.g. Schurer et al. 2013 J. Clim., 2014 Nat. Geo.). In order to separate the different forcings, it is useful to focus on a temperature change in phase with a well-documented solar minimum so as to maximize the response to this astronomical forcing. This is the approach followed by Wagner et al. (2005 Clim

  20. Muscle metabolic function and free-living physical activity.

    PubMed

    Hunter, Gary R; Larson-Meyer, D Enette; Sirikul, Bovorn; Newcomer, Bradley R

    2006-11-01

    We have previously shown that muscle metabolic function measured during exercise is related to exercise performance and subsequent 1-yr weight gain. Because it is well established that physical activity is important in weight maintenance, we examined muscle function relationships with free-living energy expenditure and physical activity. Subjects were 71 premenopausal black and white women. Muscle metabolism was evaluated by (31)P magnetic resonance spectroscopy during 90-s isometric plantar flexion contractions (45% maximum). Free-living energy expenditure (TEE) was measured using doubly labeled water, activity-related energy expenditure (AEE) was calculated as 0.9 x TEE - sleeping energy expenditure from room calorimetry, and free-living physical activity (ARTE) was calculated by dividing AEE by energy cost of standard physical activities. At the end of exercise, anaerobic glycolytic rate (ANGLY) and muscle concentration of phosphomonoesters (PME) were negatively related to TEE, AEE, and ARTE (P < 0.05). Multiple regression analysis showed that both PME (partial r = -0.29, <0.02) and ANGLY (partial r = -0.24, P < 0.04) were independently related to ARTE. PME, primarily glucose-6-phosphate and fructose-6-phosphate, was significantly related to ratings of perceived exertion (r = 0.21, P < or = 0.05) during a maximal treadmill test. PME was not related to ARTE after inclusion of RPE in the multiple regression model, suggesting that PME may be obtaining its relationship with ARTE through an increased perception of effort during physical activity. In conclusion, physically inactive individuals tend to be more dependent on anaerobic glycolysis during exercise while relying on a glycolytic pathway that may not be functioning optimally.

  1. Spatial learning-related changes in metabolic activity of limbic structures at different posttask delays.

    PubMed

    Méndez-López, M; Méndez, M; Sampedro-Piquero, P; Arias, J L

    2013-01-01

    The aim of this study was to assess the functional contribution of brain limbic system regions at different moments after the acquisition of a short-term spatial memory task performed in the Morris water maze. Adult male Wistar rats were submitted to a matching-to-sample procedure with a hidden platform. The trials were made up of two daily identical visits to the platform, sample (swim-1) and retention (swim-2). To study oxidative metabolic activity, we applied cytochrome oxidase (COx) histochemistry. Densitometric measurements were taken at 1.5, 6, 24, and 48 hr posttask. An untrained group was added to explore the COx changes not specific to the learning process. The brain regions studied showed a different pattern of metabolic activity at different time points after the spatial memory task. Specifically, a significant increase of COx was found in the septal dentate gyrus, anteromedial thalamus, medial mammillary nucleus, and entorhinal cortex at early moments after learning. The entorhinal cortex maintained an increase of COx at later stages of the posttask period. In addition, an increase of COx activity was found in the supramammillary nucleus and the retrosplenial, perirhinal, and parietal cortices a long time after learning. These findings suggest that diencephalic and cortical regions are involved in this spatial learning and contribute at different moments to process this information.

  2. Adding details to the attentional template offsets search difficulty: Evidence from contralateral delay activity.

    PubMed

    Schmidt, Joseph; Zelinsky, Gregory J

    2017-03-01

    We investigated how expected search difficultly affects the attentional template by having participants search for a teddy bear target among either other teddy bears (difficult search, high target-distractor similarity) or random nonbear objects (easy search, low target-distractor similarity). Target previews were identical in these 2 blocked conditions, and target-related visual working memory (VWM) load was measured using contralateral delay activity (CDA), an event-related potential indicating VWM load. CDA was assessed after target designation but before search display onset. Shortly after preview offset, the expectation of a difficult search produced a target-related CDA, suggesting the encoding and maintenance of target details in VWM. However, no differences in CDA were found immediately before search onset, suggesting a flexible and efficient weighting of the templates' features to reflect the expected demands of the search task. Moreover, CDA amplitude correlated with eye movement measures of search guidance in difficult search trials but not easy trials, suggesting that the utility of the attentional template is greater for more difficult searches. These findings are evidence that attentional templates depend on expected task difficulty, and that people may compensate for a more difficult search by adding details to their target representation in VWM, as measured by CDA. (PsycINFO Database Record

  3. Biological Activities of Tetrodotoxin-Producing Enterococcus faecium AD1 Isolated from Puffer Fishes.

    PubMed

    Nguyen, Tu Hoang Khue; Nguyen, Huu Ngoc; Nghe, Dat Van; Nguyen, Kim Hoang

    2015-01-01

    Puffer fishes were collected from the central sea in Vietnam from spring to summer season. The eggs were incubated in MRS broth that was used to test the toxicity in mice and isolate the lactic acid bacteria community that could produce tetrodotoxin (TTX). Thin layer chromatography (TLC) and high performance lipid chromatography (HPLC) were used to detect and quantify TTX. As a result, Enterococcus faecium AD1 which was identified by biochemical test and 16S rRNA analysis could produce TTX 0.3 mg/mL when cultured in MRS broth. The bacterium was optimized for TTX production and gave 0.18 mg/mL, 0.07 mg/mL, and 0.15 mg/mL in media prepared from the meat-washing water of freshwater fishes (Pangasius bocourti, Oreochromis sp.) and sea fish (Auxis thazard), respectively, that are also hopeful to answer some poisoning cases related to eating fishes. Enterococcus faecium also showed the wide antimicrobial activities on yeast, Gram-negative and -positive bacteria. Extracted exopolysaccharide (EPS) that reacted with 2,2-diphenyl-1-picrylhydrazyl to give IC50 at 5 mg/mL equaled 11 mg/mL ascorbic acid which could show effects on Hela-6 and Hep G2 using sulforhodamine B test. Enterococcus faecium can be claimed as a promising source in tetrodotoxin and biological compounds.

  4. Biological Activities of Tetrodotoxin-Producing Enterococcus faecium AD1 Isolated from Puffer Fishes

    PubMed Central

    Nguyen, Tu Hoang Khue; Nguyen, Huu Ngoc; Nghe, Dat Van; Nguyen, Kim Hoang

    2015-01-01

    Puffer fishes were collected from the central sea in Vietnam from spring to summer season. The eggs were incubated in MRS broth that was used to test the toxicity in mice and isolate the lactic acid bacteria community that could produce tetrodotoxin (TTX). Thin layer chromatography (TLC) and high performance lipid chromatography (HPLC) were used to detect and quantify TTX. As a result, Enterococcus faecium AD1 which was identified by biochemical test and 16S rRNA analysis could produce TTX 0.3 mg/mL when cultured in MRS broth. The bacterium was optimized for TTX production and gave 0.18 mg/mL, 0.07 mg/mL, and 0.15 mg/mL in media prepared from the meat-washing water of freshwater fishes (Pangasius bocourti, Oreochromis sp.) and sea fish (Auxis thazard), respectively, that are also hopeful to answer some poisoning cases related to eating fishes. Enterococcus faecium also showed the wide antimicrobial activities on yeast, Gram-negative and -positive bacteria. Extracted exopolysaccharide (EPS) that reacted with 2,2-diphenyl-1-picrylhydrazyl to give IC50 at 5 mg/mL equaled 11 mg/mL ascorbic acid which could show effects on Hela-6 and Hep G2 using sulforhodamine B test. Enterococcus faecium can be claimed as a promising source in tetrodotoxin and biological compounds. PMID:26380310

  5. Cytosolic calcium coordinates mitochondrial energy metabolism with presynaptic activity.

    PubMed

    Chouhan, Amit K; Ivannikov, Maxim V; Lu, Zhongmin; Sugimori, Mutsuyuki; Llinas, Rodolfo R; Macleod, Gregory T

    2012-01-25

    Most neurons fire in bursts, imposing episodic energy demands, but how these demands are coordinated with oxidative phosphorylation is still unknown. Here, using fluorescence imaging techniques on presynaptic termini of Drosophila motor neurons (MNs), we show that mitochondrial matrix pH (pHm), inner membrane potential (Δψm), and NAD(P)H levels ([NAD(P)H]m) increase within seconds of nerve stimulation. The elevations of pHm, Δψm, and [NAD(P)H]m indicate an increased capacity for ATP production. Elevations in pHm were blocked by manipulations that blocked mitochondrial Ca2+ uptake, including replacement of extracellular Ca2+ with Sr2+ and application of either tetraphenylphosphonium chloride or KB-R7943, indicating that it is Ca2+ that stimulates presynaptic mitochondrial energy metabolism. To place this phenomenon within the context of endogenous neuronal activity, the firing rates of a number of individually identified MNs were determined during fictive locomotion. Surprisingly, although endogenous firing rates are significantly different, there was little difference in presynaptic cytosolic Ca2+ levels ([Ca2+]c) between MNs when each fires at its endogenous rate. The average [Ca2+]c level (329±11 nM) was slightly above the average Ca2+ affinity of the mitochondria (281±13 nM). In summary, we show that when MNs fire at endogenous rates, [Ca2+]c is driven into a range where mitochondria rapidly acquire Ca2+. As we also show that Ca2+ stimulates presynaptic mitochondrial energy metabolism, we conclude that [Ca2+]c levels play an integral role in coordinating mitochondrial energy metabolism with presynaptic activity in Drosophila MNs.

  6. Cytosolic Calcium Coordinates Mitochondrial Energy Metabolism with Presynaptic Activity

    PubMed Central

    Chouhan, Amit K.; Ivannikov, Maxim V.; Lu, Zhongmin; Sugimori, Mutsuyuki; Llinas, Rodolfo R.; Macleod, Gregory T.

    2012-01-01

    Most neurons fire in bursts, imposing episodic energy demands, but how these demands are coordinated with oxidative phosphorylation is still unknown. Here, using fluorescence imaging techniques on presynaptic termini of Drosophila motor neurons (MNs), we show that mitochondrial matrix pH (pHm), inner membrane potential (Δψm), and NAD(P)H levels ([NAD(P)H]m) increase within seconds of nerve stimulation. The elevations of pHm, Δψm, and [NAD(P)H]m indicate an increased capacity for ATP production. Elevations in pHm were blocked by manipulations which blocked mitochondrial Ca2+ uptake, including replacement of extracellular Ca2+ with Sr2+, and application of either tetraphenylphosphonium chloride or KB-R7943, indicating that it is Ca2+ that stimulates presynaptic mitochondrial energy metabolism. To place this phenomenon within the context of endogenous neuronal activity, the firing rates of a number of individually identified MNs were determined during fictive locomotion. Surprisingly, although endogenous firing rates are significantly different, there was little difference in presynaptic cytosolic Ca2+ levels ([Ca2+]c) between MNs when each fires at its endogenous rate. The average [Ca2+]c level (329±11nM) was slightly above the average Ca2+ affinity of the mitochondria (281±13nM). In summary, we show that when MNs fire at endogenous rates [Ca2+]c is driven into a range where mitochondria rapidly acquire Ca2+. As we also show that Ca2+ stimulates presynaptic mitochondrial energy metabolism, we conclude that [Ca2+]c levels play an integral role in coordinating mitochondrial energy metabolism with presynaptic activity in Drosophila MNs. PMID:22279208

  7. Metabolic Equivalent in Adolescents, Active Adults and Pregnant Women

    PubMed Central

    Melzer, Katarina; Heydenreich, Juliane; Schutz, Yves; Renaud, Anne; Kayser, Bengt; Mäder, Urs

    2016-01-01

    Metabolic Equivalent” (MET) represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O2/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry) were measured in adolescent males (n = 50) and females (n = 50), women during pregnancy (gestation week 35–41, n = 46), women 24–53 weeks postpartum (n = 27), and active men (n = 30), and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h) was significantly higher than that of adolescent females (1.11 kcal/kg × h), with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h) and overweight (0.89 kcal/kg × h) adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard. PMID:27447667

  8. 3xTg-AD Mice Exhibit an Activated Central Stress Axis during Early-Stage Pathology

    PubMed Central

    Hebda-Bauer, Elaine K.; Simmons, Tracy A.; Sugg, Andrew; Ural, Eren; Stewart, James A.; Beals, James L.; Wei, Qiang; Watson, Stanley J.; Akil, Huda

    2012-01-01

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in response to the organism’s innate need for homeostasis. The glucocorticoids (GCs) that are released into the circulation upon acute activation of the HPA axis perform stress-adaptive functions and provide negative feedback to turn off the HPA axis, but can be detrimental when in excess. Long-term activation of the HPA axis (such as with chronic stress) enhances susceptibility to neuronal dysfunction and death, and increases vulnerability to Alzheimer’s disease (AD). However, little is known how components of the HPA axis, upstream of GCs, impact vulnerability to AD. This study examined basal gene expression of stress-related molecules in brains of 3xTg-AD mice during early-stage pathology. Basal glucocorticoid levels and mRNA expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and corticotropic releasing hormone (CRH) in several stress- and emotionality-related brain regions were measured in 3–4-month-old 3xTg-AD mice. Despite normal glucocorticoid levels, young 3xTg-AD mice exhibit an activated central HPA axis, with altered mRNA levels of MR and GR in the hippocampus, GR and CRH in the paraventricular nucleus of the hypothalamus, GR and CRH in the central nucleus of the amygdala, and CRH in the bed nucleus of the stria terminalis. This HPA axis activation is present during early-stage neuropathology when 3xTg-AD mice show mild behavioral changes, suggesting an ongoing neuroendocrine regulation that precedes the onset of severe AD-like pathology and behavioral deficits. PMID:22976078

  9. Brain Hyperglycemia Induced by Heroin: Association with Metabolic Neural Activation.

    PubMed

    Solis, Ernesto; Bola, R Aaron; Fasulo, Bradley J; Kiyatkin, Eugene A

    2017-02-15

    Glucose enters the brain extracellular space from arterial blood, and its proper delivery is essential for metabolic activity of brain cells. By using enzyme-based biosensors coupled with high-speed amperometry in freely moving rats, we previously showed that glucose levels in the nucleus accumbens (NAc) display high variability, increasing rapidly following exposure to various arousing stimuli. In this study, the same technology was used to assess NAc glucose fluctuations induced by intravenous heroin. Heroin passively injected at a low dose optimal for maintaining self-administration behavior (100 μg/kg) induces a rapid but moderate glucose rise (∼150-200 μM or ∼15-25% over resting baseline). When the heroin dose was doubled and tripled, the increase became progressively larger in magnitude and longer in duration. Heroin-induced glucose increases also occurred in other brain structures (medial thalamus, lateral striatum, hippocampus), suggesting that brain hyperglycemia is a whole-brain phenomenon but changes were notably distinct in each structure. While local vasodilation appears to be the possible mechanism underlying the rapid rise in extracellular glucose levels, the driving factor for this vasodilation (central vs peripheral) remains to be clarified. The heroin-induced NAc glucose increases positively correlated with increases in intracerebral heat production determined in separate experiments using multisite temperature recordings (NAc, temporal muscle and skin). However, glucose levels rise very rapidly, preceding much slower increases in brain heat production, a measure of metabolic activation associated with glucose consumption.

  10. Metabolic pathways in immune cell activation and quiescence.

    PubMed

    Pearce, Erika L; Pearce, Edward J

    2013-04-18

    Studies of immune system metabolism ("immunometabolism") segregate along two paths. The first investigates the effects of immune cells on organs that regulate whole-body metabolism, such as adipose tissue and liver. The second explores the role of metabolic pathways within immune cells and how this regulates immune response outcome. Distinct metabolic pathways diverge and converge at many levels, and, therefore, cells face choices as to how to achieve their metabolic goals. There is interest in fully understanding how and why immune cells commit to particular metabolic fates and in elucidating the immunologic consequences of reaching a metabolic endpoint by one pathway versus another. This is particularly intriguing, given that metabolic commitment is influenced not only by substrate availability but also by signaling pathways elicited by metabolites. Thus, metabolic choices in cells enforce fate and function, and this area will be the subject of this review.

  11. Effects of increased transaldolase activity on D-xylulose and D-glucose metabolism in Saccharomyces cerevisiae cell extracts.

    PubMed Central

    Senac, T; Hahn-Hägerdal, B

    1991-01-01

    In vitro metabolism of D-xylulose and D-glucose in extracts obtained from D-glucose- and D-xylulose-fermenting Saccharomyces cerevisiae cells was investigated with 10- and 100-fold-increased activity of the enzyme transaldolase (EC 2.2.1.2). The rate of sugar consumption was the same in most cases, whereas the rate of ethanol formation decreased with increased levels of transaldolase. The formation of glycerol, pentitols, and acetic acid was not dependent on added transaldolase but was dependent on the sugar used as the growth substrate and on the sugar used in the in vitro metabolism experiments. The carbon balance showed that the dissimilated carbon could not be accounted for in products when transaldolase was added. The concentration of D-fructose-1,6.-diphosphate in the extracts was not influenced by added transaldolase but was higher with D-xylulose than with D-glucose. Levels of pyruvate, comparable with the two substrates, decreased with increasing levels of transaldolase. Exogenously added transaldolase decreased D-sedoheptulose-7-phosphate levels when D-xylulose was the substrate. The results are discussed in relation to the dissimilation of carbon through the upper part of glycolysis and the pentose phosphate pathway. PMID:1831338

  12. Carboxylesterase 1 as a determinant of clopidogrel metabolism and activation.

    PubMed

    Zhu, Hao-Jie; Wang, Xinwen; Gawronski, Brian E; Brinda, Bryan J; Angiolillo, Dominick J; Markowitz, John S

    2013-03-01

    Clopidogrel pharmacotherapy is associated with substantial interindividual variability in clinical response, which can translate into an increased risk of adverse outcomes. Clopidogrel, a recognized substrate of hepatic carboxylesterase 1 (CES1), undergoes extensive hydrolytic metabolism in the liver. Significant interindividual variability in the expression and activity of CES1 exists, which is attributed to both genetic and environmental factors. We determined whether CES1 inhibition and CES1 genetic polymorphisms would significantly influence the biotransformation of clopidogrel and alter the formation of the active metabolite. Coincubation of clopidogrel with the CES1 inhibitor bis(4-nitrophenyl) phosphate in human liver s9 fractions significantly increased the concentrations of clopidogrel, 2-oxo-clopidogrel, and clopidogrel active metabolite, while the concentrations of all formed carboxylate metabolites were significantly decreased. As anticipated, clopidogrel and 2-oxo-clopidogrel were efficiently hydrolyzed by the cell s9 fractions prepared from wild-type CES1 transfected cells. The enzymatic activity of the CES1 variants G143E and D260fs were completely impaired in terms of catalyzing the hydrolysis of clopidogrel and 2-oxo-clopidogrel. However, the natural variants G18V, S82L, and A269S failed to produce any significant effect on CES1-mediated hydrolysis of clopidogrel or 2-oxo-clopidogrel. In summary, deficient CES1 catalytic activity resulting from CES1 inhibition or CES1 genetic variation may be associated with higher plasma concentrations of clopidogrel-active metabolite, and hence may enhance antiplatelet activity. Additionally, CES1 genetic variants have the potential to serve as a biomarker to predict clopidogrel response and individualize clopidogrel dosing regimens in clinical practice.

  13. Control of macrophage metabolism and activation by mTOR and Akt signaling

    PubMed Central

    Covarrubias, Anthony J.; Aksoylar, H. Ibrahim; Horng, Tiffany

    2015-01-01

    Macrophages are pleiotropic cells that assume a variety of functions depending on their tissue of residence and tissue state. They maintain homeostasis as well as coordinate responses to stresses such as infection and metabolic challenge. The ability of macrophages to acquire diverse, context-dependent activities requires their activation (or polarization) to distinct functional states. While macrophage activation is well understood at the level of signal transduction and transcriptional regulation, the metabolic underpinnings are poorly understood. Importantly, emerging studies indicate that metabolic shifts play a pivotal role in control of macrophage activation and acquisition of context-dependent effector activities. The signals that drive macrophage activation impinge on metabolic pathways, allowing for coordinate control of macrophage activation and metabolism. Here we discuss how mTOR and Akt, major metabolic regulators and targets of such activation signals, control macrophage metabolism and activation. Dysregulated macrophage activities contribute to many diseases, including infectious, inflammatory, and metabolic diseases and cancer, thus a better understanding of metabolic control of macrophage activation could pave the way to the development of new therapeutic strategies. PMID:26360589

  14. Control of macrophage metabolism and activation by mTOR and Akt signaling.

    PubMed

    Covarrubias, Anthony J; Aksoylar, H Ibrahim; Horng, Tiffany

    2015-08-01

    Macrophages are pleiotropic cells that assume a variety of functions depending on their tissue of residence and tissue state. They maintain homeostasis as well as coordinate responses to stresses such as infection and metabolic challenge. The ability of macrophages to acquire diverse, context-dependent activities requires their activation (or polarization) to distinct functional states. While macrophage activation is well understood at the level of signal transduction and transcriptional regulation, the metabolic underpinnings are poorly understood. Importantly, emerging studies indicate that metabolic shifts play a pivotal role in control of macrophage activation and acquisition of context-dependent effector activities. The signals that drive macrophage activation impinge on metabolic pathways, allowing for coordinate control of macrophage activation and metabolism. Here we discuss how mTOR and Akt, major metabolic regulators and targets of such activation signals, control macrophage metabolism and activation. Dysregulated macrophage activities contribute to many diseases, including infectious, inflammatory, and metabolic diseases and cancer, thus a better understanding of metabolic control of macrophage activation could pave the way to the development of new therapeutic strategies.

  15. Macroautophagy regulates energy metabolism during effector T cell activation.

    PubMed

    Hubbard, Vanessa M; Valdor, Rut; Patel, Bindi; Singh, Rajat; Cuervo, Ana Maria; Macian, Fernando

    2010-12-15

    Macroautophagy is a highly conserved mechanism of lysosomal-mediated protein degradation that plays a key role in maintaining cellular homeostasis by recycling amino acids, reducing the amount of damaged proteins, and regulating protein levels in response to extracellular signals. We have found that macroautophagy is induced after effector T cell activation. Engagement of the TCR and CD28 results in enhanced microtubule-associated protein 1 light chain 3 (LC3) processing, increased numbers of LC3-containing vesicles, and increased LC3 flux, indicating active autophagosome formation and clearance. The autophagosomes formed in stimulated T cells actively fuse with lysosomes to degrade their cargo. Using a conditional KO mouse model where Atg7, a critical gene for macroautophagy, is specifically deleted in T cells, we have found that macroautophagy-deficient effector Th cells have defective IL-2 and IFN-γ production and reduced proliferation after stimulation, with no significant increase in apoptosis. We have found that ATP generation is decreased when autophagy is blocked, and defects in activation-induced cytokine production are restored when an exogenous energy source is added to macroautophagy-deficient T cells. Furthermore, we present evidence showing that the nature of the cargo inside autophagic vesicles found in resting T cells differs from the cargo of autophagosomes in activated T cells, where mitochondria and other organelles are selectively excluded. These results suggest that macroautophagy is an actively regulated process in T cells that can be induced in response to TCR engagement to accommodate the bioenergetic requirements of activated T cells.

  16. INCREASED ENDOCRINE ACTIVITY OF XENOBIOTIC CHEMICALS AS MEDIATED BY METABOLIC ACTIVATION

    EPA Science Inventory

    This research is part of an effort to develop in vitro assays and QSARs applicable to untested chemicals on EPA inventories through study of estrogen receptor (ER) binding and estrogen mediated gene expression in fish. The current effort investigates metabolic activation of chemi...

  17. The relationship between physical activity levels and metabolic syndrome in male white-collar workers

    PubMed Central

    Ko, Kwang-Jun; Kim, Eon-Ho; Baek, Un-Hyo; Gang, Zhao; Kang, Seol-Jung

    2016-01-01

    [Purpose] Physical activity is important for preventing and managing metabolic syndrome. White-collar workers can be inherently predisposed to chronic diseases, as their jobs are primarily sedentary. The purpose of this study was to examine the relationship between physical activity and metabolic syndrome in male white-collar workers. [Subjects and Methods] Physical activity and metabolic syndrome factors were measured in 331 male public office workers. Physical activity was classified as high (N=101), moderate (N=115), or low (N=111) using the International Physical Activity Questionnaire. To diagnose metabolic syndrome, the U.S. National Cholesterol Education Program’s standard was used. [Results] Waist circumference and triglyceride levels, factors of metabolic syndrome, were significantly higher in the low physical activity group than in the moderate or high activity group. High-density lipoprotein cholesterol was significantly lower in the low physical activity group than in the moderate or high activity group. Waist circumference and fasting glucose were negatively correlated with physical activity level, and HDL cholesterol showed a positive correlation with waist circumference. The odds ratios for metabolic syndrome were 2.03 times higher (95% confidence interval, 1.01–4.09) in the low physical activity group than in the high physical activity group. [Conclusion] Low physical activity was a risk factor for metabolic syndrome in white-collar workers. Therefore, increasing physical activity in daily life may prevent metabolic syndrome in white-collar workers. PMID:27942116

  18. The relationship between physical activity levels and metabolic syndrome in male white-collar workers.

    PubMed

    Ko, Kwang-Jun; Kim, Eon-Ho; Baek, Un-Hyo; Gang, Zhao; Kang, Seol-Jung

    2016-11-01

    [Purpose] Physical activity is important for preventing and managing metabolic syndrome. White-collar workers can be inherently predisposed to chronic diseases, as their jobs are primarily sedentary. The purpose of this study was to examine the relationship between physical activity and metabolic syndrome in male white-collar workers. [Subjects and Methods] Physical activity and metabolic syndrome factors were measured in 331 male public office workers. Physical activity was classified as high (N=101), moderate (N=115), or low (N=111) using the International Physical Activity Questionnaire. To diagnose metabolic syndrome, the U.S. National Cholesterol Education Program's standard was used. [Results] Waist circumference and triglyceride levels, factors of metabolic syndrome, were significantly higher in the low physical activity group than in the moderate or high activity group. High-density lipoprotein cholesterol was significantly lower in the low physical activity group than in the moderate or high activity group. Waist circumference and fasting glucose were negatively correlated with physical activity level, and HDL cholesterol showed a positive correlation with waist circumference. The odds ratios for metabolic syndrome were 2.03 times higher (95% confidence interval, 1.01-4.09) in the low physical activity group than in the high physical activity group. [Conclusion] Low physical activity was a risk factor for metabolic syndrome in white-collar workers. Therefore, increasing physical activity in daily life may prevent metabolic syndrome in white-collar workers.

  19. Metaproteomic analysis reveals microbial metabolic activities in the deep ocean

    NASA Astrophysics Data System (ADS)

    Wang, Da-Zhi; Xie, Zhang-Xian; Zhang, Shu-Feng; Wang, Ming-Hua; Zhang, Hao; Kong, Ling-Fen; Lin, Lin

    2016-04-01

    The deep sea is the largest habitat on earth and holds many and varied microbial life forms. However, little is known about their metabolic activities in the deep ocean. Here, we characterized protein profiles of particulate (>0.22 μm) and dissolved (between 10 kDa and 0.22 μm) fractions collected from the deep South China Sea using a shotgun proteomic approach. SAR324, Alteromonadales and SAR11 were the most abundant groups, while Prasinophyte contributed most to eukaryotes and cyanophage to viruses. The dominant heterotrophic activity was evidenced by the abundant transporters (33%). Proteins participating in nitrification, methanogenesis, methyltrophy and CO2 fixation were detected. Notably, the predominance of unique cellular proteins in dissolved fraction suggested the presence of membrane structures. Moreover, the detection of translation proteins related to phytoplankton indicated that other process rather than sinking particles might be the downward export of living cells. Our study implied that novel extracellular activities and the interaction of deep water with its overlying water could be crucial to the microbial world of deep sea.

  20. Phenomenological correlates of metabolic activity in 18 patients with chronic schizophrenia

    SciTech Connect

    Volkow, N.D.; Wolf, A.P.; Van Gelder, P.; Brodie, J.D.; Overall, J.E.; Cancro, R.; Gomez-Mont, F.

    1987-02-01

    Using (11C)-deoxy-D-glucose and positron emission tomography (PET), the authors measured brain metabolism in 18 patients with chronic schizophrenia to assess which of the metabolic measures from two test conditions was more closely related to the patients' differing clinical characteristics. The two conditions were resting and activation, and an eye tracking task was used. Patients with more negative symptoms showed lower global metabolic rates and more severe hypofrontality than did the patients with fewer negative symptoms. Differences among the patients were distinguished by the task: sicker patients failed to show a metabolic activation response. These findings suggest that cerebral metabolic patterns reflect clinical characteristics of schizophrenic patients.

  1. The metabolic activator FOXO1 binds hepatitis B virus DNA and activates its transcription

    SciTech Connect

    Shlomai, Amir; Shaul, Yosef

    2009-04-17

    Hepatitis B virus (HBV) is a small DNA virus that targets the liver and infects humans worldwide. Recently we have shown that the metabolic regulator PGC-1{alpha} coactivates HBV transcription thereby rendering the virus susceptible to fluctuations in the nutritional status of the liver. PGC-1{alpha} coactivation of HBV is mediated through the liver-enriched nuclear receptor HNF4{alpha} and through another yet unknown transcription factor(s). Here we show that the forkhead transcription factor FOXO1, a known target for PGC-1{alpha} coactivation and a central mediator of glucose metabolism in the liver, binds HBV core promoter and activates its transcription. This activation is further enhanced in the presence of PGC-1{alpha}, implying that FOXO1 is a target for PGC-1{alpha} coactivation of HBV transcription. Thus, our results identify another key metabolic regulator as an activator of HBV transcription, thereby supporting the principle that HBV gene expression is regulated in a similar way to key hepatic metabolic genes.

  2. Metabolism

    MedlinePlus

    ... and intestines. Several of the hormones of the endocrine system are involved in controlling the rate and direction ... For Kids For Parents MORE ON THIS TOPIC Endocrine System What Can I Do About My High Metabolism? ...

  3. Metabolism

    MedlinePlus

    ... symptoms. Metabolic diseases and conditions include: Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism is caused ... or through surgery or radiation treatments. Hypothyroidism (pronounced: hi-po-THIGH-roy-dih-zum). Hypothyroidism is caused ...

  4. Effect of sodium azide on the metabolic activity of cultured fetal cells.

    PubMed

    Ishikawa, Takaki; Zhu, Bao-Li; Maeda, Hitoshi

    2006-09-01

    Sodium azide is a highly toxic substance. However, the mechanism of its toxicity has not been fully established. In the present study, we attempted to investigate the toxicity of sodium azide in various cultured fetal cells, using changes in cellular respiration as an indicator of metabolic inhibition to elucidate tissue-specificity. The human fetal cell lines used in this study included myocardial cells, nerve cells, fibroblasts, hepatocytes and renal tubular epithelial cells. The cells were seeded in wells at a density of 2 x 10(6)cells/2mL, sodium azide was added at a concentration of 0.01 ng/mL to 10 microg/mL, and the respiration of each type of cell was measured 1 h later using a dissolved oxygen meter. The concentration at which sodium azide inhibited metabolic activity was lower in the nerve and myocardial cells than in the fibroblasts, hepatocytes and renal tubular epithelial cells. These findings may serve to clarify the dynamic mechanisms of sodium azide toxicity in vivo.

  5. Metabolic Activity and Energy Charge of Excised Maize Root Tips under Anoxia

    PubMed Central

    Saglio, Pierre H.; Raymond, Philippe; Pradet, Alain

    1980-01-01

    Energy charge and fermentative metabolism under anoxia were monitored in excised maize root tips after various times of aging in air and were related to their soluble sugar content. The energy charge value, which was 0.9 in air irrespective of the time of aging, dropped to a lower value within minutes of transfer to a nitrogen atmosphere. This value was dependent upon sugar content of the tissues which was itself a function of aging. The energy charge value after transfer to nitrogen was 0.6 in freshly excised tissue but only 0.2 in tissue aged for 4 hours. When aged tissues supplied with 0.2 molar glucose were transferred to nitrogen, the energy charge was 0.6, irrespective of the time of aging. When 0.2 molar glucose was added under nitrogen, energy charge rose to 0.6. This rise was faster in root tips aged for 8 hours than those aged for 24 hours. The rate of ethanol plus lactate production (representing 60 and 10%, respectively, of the total sugar consumption in anoxia) was closely correlated to the level of energy charge. It is concluded that, in anoxia, there is a quantitative relationship between the energy charge value and the level of metabolic activity via fermentative pathways. PMID:16661575

  6. Proteome analysis of Aspergillus niger: Lactate added in starch-containing medium can increase production of the mycotoxin fumonisin B2 by modifying acetyl-CoA metabolism

    PubMed Central

    2009-01-01

    Background Aspergillus niger is a filamentous fungus found in the environment, on foods and feeds and is used as host for production of organic acids, enzymes and proteins. The mycotoxin fumonisin B2 was recently found to be produced by A. niger and hence very little is known about production and regulation of this metabolite. Proteome analysis was used with the purpose to reveal how fumonisin B2 production by A. niger is influenced by starch and lactate in the medium. Results Fumonisin B2 production by A. niger was significantly increased when lactate and starch were combined in the medium. Production of a few other A. niger secondary metabolites was affected similarly by lactate and starch (fumonisin B4, orlandin, desmethylkotanin and pyranonigrin A), while production of others was not (ochratoxin A, ochratoxin alpha, malformin A, malformin C, kotanin, aurasperone B and tensidol B). The proteome of A. niger was clearly different during growth on media containing 3% starch, 3% starch + 3% lactate or 3% lactate. The identity of 59 spots was obtained, mainly those showing higher or lower expression levels on medium with starch and lactate. Many of them were enzymes in primary metabolism and other processes that affect the intracellular level of acetyl-CoA or NADPH. This included enzymes in the pentose phosphate pathway, pyruvate metabolism, the tricarboxylic acid cycle, ammonium assimilation, fatty acid biosynthesis and oxidative stress protection. Conclusions Lactate added in a medium containing nitrate and starch can increase fumonisin B2 production by A. niger as well as production of some other secondary metabolites. Changes in the balance of intracellular metabolites towards a higher level of carbon passing through acetyl-CoA and a high capacity to regenerate NADPH during growth on medium with starch and lactate were found to be the likely cause of this effect. The results lead to the hypothesis that fumonisin production by A. niger is regulated by acetyl

  7. Alzheimer's as a metabolic disease.

    PubMed

    Demetrius, Lloyd A; Driver, Jane

    2013-12-01

    Empirical evidence indicates that impaired mitochondrial energy metabolism is the defining characteristic of almost all cases of Alzheimer's disease (AD). Evidence is reviewed supporting the general hypothesis that the up-regulation of OxPhos activity, a metabolic response to mitochondrial dysregulation, drives the cascade of events leading to AD. This mode of metabolic alteration, called the Inverse Warburg effect, is postulated as an essential compensatory mechanism of energy production to maintain the viability of impaired neuronal cells. This article appeals to the inverse comorbidity of cancer and AD to show that the amyloid hypothesis, a genetic and neuron-centric model of the origin of sporadic forms of AD, is not consistent with epidemiological data concerning the age-incidence rates of AD. A view of Alzheimer's as a metabolic disease-a condition consistent with mitochondrial dysregulation and the Inverse Warburg effect, will entail a radically new approach to diagnostic and therapeutic strategies.

  8. Bioirrigation impacts on sediment respiration and microbial metabolic activity

    NASA Astrophysics Data System (ADS)

    Baranov, V. A.; Lewandowski, J.; Romeijn, P.; Krause, S.

    2015-12-01

    Some bioturbators build tubes in the sediment and pump water through their burrows (ventilation). Oxygen is transferred through the burrow walls in the adjacent sediment (bioirrigation). Bioirrigation is playing a pivotal role in the mediation of biogeochemical processes in lake sediments and has the potential to enhance nutrient cycling. The present study investigates the impact of bioirrigation on lake sediment metabolism, respiration rates and in particular, the biogeochemical impacts of bioirrigation intensity as a function of organism density. We therefore apply the bioreactive Resazurin/Resorufin smart tracer system for quantifying the impact of different densities of Chironomidae (Diptera) larvae (0-2112 larvae/m2) on lake sediment respiration in a microcosm experiment. Tracer decay has been found to be proportional to the amount of the aerobic respiration at the sediment-water interface. Tracer transformation was in good agreement with Chironomidae density (correlation, r=0.9). Tracer transformation rates (and sediment respiration) were found to be correlated to Chironomidae density, with highest transformation rates observed in the microcosms with highest density of 2112 larvae/m2. This relationship was not linear though, with sediment respiration rates at the highest larvae densities declining from the linear trend predicted from lower and intermediate larvae density-respiration relationships. We interpret this effect as a density dependent suppression of the Chironomid's metabolic activity. The observations of this study have implications for eutrophied lakes with high densities of bioirrigators. Despite high density of bioirrigirrigating benthos, mineralization of the organic matter in such habitats would likely be lower than in lakes with intermediate densities of the bioturbators.

  9. Metabolic signals and innate immune activation in obesity and exercise.

    PubMed

    Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

    2015-01-01

    The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities.

  10. Metabolic activity of permafrost bacteria below the freezing point

    NASA Technical Reports Server (NTRS)

    Rivkina, E. M.; Friedmann, E. I.; McKay, C. P.; Gilichinsky, D. A.

    2000-01-01

    Metabolic activity was measured in the laboratory at temperatures between 5 and -20 degrees C on the basis of incorporation of (14)C-labeled acetate into lipids by samples of a natural population of bacteria from Siberian permafrost (permanently frozen soil). Incorporation followed a sigmoidal pattern similar to growth curves. At all temperatures, the log phase was followed, within 200 to 350 days, by a stationary phase, which was monitored until the 550th day of activity. The minimum doubling times ranged from 1 day (5 degrees C) to 20 days (-10 degrees C) to ca. 160 days (-20 degrees C). The curves reached the stationary phase at different levels, depending on the incubation temperature. We suggest that the stationary phase, which is generally considered to be reached when the availability of nutrients becomes limiting, was brought on under our conditions by the formation of diffusion barriers in the thin layers of unfrozen water known to be present in permafrost soils, the thickness of which depends on temperature.

  11. Metabolic Activity of Permafrost Bacteria below the Freezing Point

    PubMed Central

    Rivkina, E. M.; Friedmann, E. I.; McKay, C. P.; Gilichinsky, D. A.

    2000-01-01

    Metabolic activity was measured in the laboratory at temperatures between 5 and −20°C on the basis of incorporation of 14C-labeled acetate into lipids by samples of a natural population of bacteria from Siberian permafrost (permanently frozen soil). Incorporation followed a sigmoidal pattern similar to growth curves. At all temperatures, the log phase was followed, within 200 to 350 days, by a stationary phase, which was monitored until the 550th day of activity. The minimum doubling times ranged from 1 day (5°C) to 20 days (−10°C) to ca. 160 days (−20°C). The curves reached the stationary phase at different levels, depending on the incubation temperature. We suggest that the stationary phase, which is generally considered to be reached when the availability of nutrients becomes limiting, was brought on under our conditions by the formation of diffusion barriers in the thin layers of unfrozen water known to be present in permafrost soils, the thickness of which depends on temperature. PMID:10919774

  12. [TV, overweight and nutritional surveillance. Ads content, food intake and physical activity].

    PubMed

    Spagnoli, T D; Bioletti, L; Bo, C; Formigatti, M

    2003-01-01

    The relationship between television viewing and obesity in children and adults was examined in a large number of cross-sectional epidemiological studies. Some randomised, controlled trials confirmed the evidence that television viewing is a cause of increased body fatness. It seems of utility in nutritional surveillance to esteem time spent by children and adults in television watching and to evaluate ads contents and food preferences suggested by them. This editorial shows a two-years long analysis of food commercials broadcasted by the main Italian TV networks; food ads targeted on children, housewives and sport fans were evaluated; the relationship between television viewing, commercials and food intake or global lifestyle was investigated in a Piedmont's population (from Northern Italy). School projects aimed to reduce television viewing represent a promising strategy for preventing childhood obesity.

  13. Development of a highly sensitive cytotoxicity assay system for CYP3A4-mediated metabolic activation.

    PubMed

    Hosomi, Hiroko; Fukami, Tatsuki; Iwamura, Atsushi; Nakajima, Miki; Yokoi, Tsuyoshi

    2011-08-01

    Drug-induced hepatotoxicity, which is a rare but serious adverse reaction to a large number of pharmaceutical drugs, is sometimes associated with reactive metabolites produced by drug-metabolizing enzymes. In the present study, we constructed a cell-based system to evaluate the cytotoxicity of reactive metabolites produced by CYP3A4 using human hepatoma cells infected with an adenovirus vector expressing human CYP3A4 (AdCYP3A4). When seven hepatoma cell lines (HepG2, Hep3B, HLE, HLF, Huh6, Huh7, and Fa2N4 cells) were infected with AdCYP3A4, HepG2 cells showed the highest CYP3A4 protein expression and testosterone 6β-hydroxylase activity (670 pmol · min(-1) · mg(-1)). With the use of AdCYP3A4-infected HepG2 cells, the cytotoxicities of 23 drugs were evaluated by the 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt assay, and the cell viability when treated with 11 drugs (amiodarone, desipramine, felbamate, isoniazid, labetalol, leflunomide, nefazodone, nitrofurantoin, tacrine, terbinafine, and tolcapone) was significantly decreased. Moreover, the transfection of siRNA for nuclear factor erythroid 2-related factor 2 (Nrf2) to decrease the cellular expression level of Nrf2 exacerbated the cytotoxicity of some drugs (troglitazone, flutamide, acetaminophen, clozapine, terbinafine, and desipramine), suggesting that the genes regulated by Nrf2 are associated with the detoxification of the cytotoxicities mediated by CYP3A4. We constructed a highly sensitive cell-based system to detect the drug-induced cytotoxicity mediated by CYP3A4. This system would be beneficial in preclinical screening in drug development and increase our understanding of the drug-induced cytotoxicity associated with CYP3A4.

  14. Statins enhance peroxisome proliferator-activated receptor gamma coactivator-1alpha activity to regulate energy metabolism.

    PubMed

    Wang, Wenxian; Wong, Chi-Wai

    2010-03-01

    Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) serves as an inducible coactivator for a number of transcription factors to control energy metabolism. Insulin signaling through Akt kinase has been demonstrated to phosphorylate PGC-1alpha at serine 571 and downregulate its activity in the liver. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that reduce cholesterol synthesis in the liver. In this study, we found that statins reduced the active form of Akt and enhanced PGC-1alpha activity. Specifically, statins failed to activate an S571A mutant of PGC-1alpha. The activation of PGC-1alpha by statins selectively enhanced the expression of energy metabolizing enzymes and regulators including peroxisome proliferator-activated receptor alpha, acyl-CoA oxidase, carnitine palmitoyl transferase-1A, and pyruvate dehydrogenase kinase 4. Importantly, a constitutively active form of Akt partially reduced the statin-enhanced gene expression. Our study thus provides a plausible mechanistic explanation for the hypolipidemic effect of statin through elevating the rate of beta-oxidation and mitochondrial Kreb's cycle capacity to enhance fatty acid utilization while reducing the rate of glycolysis.

  15. Mitochondrial biogenesis and proteome remodeling promotes one carbon metabolism for T cell activation

    PubMed Central

    Ron-Harel, Noga; Santos, Daniel; Ghergurovich, Jonathan M.; Sage, Peter T.; Reddy, Anita; Lovitch, Scott B.; Dephoure, Noah; Satterstrom, F. Kyle; Sheffer, Michal; Spinelli, Jessica B.; Gygi, Steven; Rabinowitz, Joshua D.; Sharpe, Arlene H.; Haigis, Marcia C.

    2017-01-01

    Summary Naïve T cell stimulation activates anabolic metabolism to fuel the transition from quiescence to growth and proliferation. Here we show that naïve CD4+ T cell activation induces a unique program of mitochondrial biogenesis and remodeling. Using mass spectrometry, we quantified protein dynamics during T cell activation. We identified substantial remodeling of the mitochondrial proteome over the first 24 hr of T cell activation to generate mitochondria with a distinct metabolic signature, with one carbon metabolism as the most induced pathway. Salvage pathways and mitochondrial one carbon metabolism, fed by serine, contribute to purine and thymidine synthesis to enable T cell proliferation and survival. Genetic inhibition of the mitochondrial serine catabolic enzyme SHMT2 impaired T cell survival in culture, and antigen-specific T cell abundance in vivo. Thus, during T cell activation, mitochondrial proteome remodeling generates specialized mitochondria with enhanced one carbon metabolism that is critical for T cell activation and survival. PMID:27411012

  16. Metabolic and Cardiovascular Responses of Children during Prolonged Physical Activity.

    ERIC Educational Resources Information Center

    Chausow, Sharon A.; And Others

    1984-01-01

    Metabolic and cardiovascular responses during 45 minutes of continuous moderate intensity exercise were investigated in 11 children, 8-11 years of age. Results indicate that children exhibit metabolic and cardiovascular adjustments similar to those noted in adults during prolonged exercise. (Author/JMK)

  17. Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR.

    PubMed

    Calkin, Anna C; Tontonoz, Peter

    2012-03-14

    Nuclear receptors are integrators of hormonal and nutritional signals, mediating changes to metabolic pathways within the body. Given that modulation of lipid and glucose metabolism has been linked to diseases including type 2 diabetes, obesity and atherosclerosis, a greater understanding of pathways that regulate metabolism in physiology and disease is crucial. The liver X receptors (LXRs) and the farnesoid X receptors (FXRs) are activated by oxysterols and bile acids, respectively. Mounting evidence indicates that these nuclear receptors have essential roles, not only in the regulation of cholesterol and bile acid metabolism but also in the integration of sterol, fatty acid and glucose metabolism.

  18. Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR

    PubMed Central

    2013-01-01

    Nuclear receptors are integrators of hormonal and nutritional signals, mediating changes to metabolic pathways within the body. Given that modulation of lipid and glucose metabolism has been linked to diseases including type 2 diabetes, obesity and atherosclerosis, a greater understanding of pathways that regulate metabolism in physiology and disease is crucial. The liver X receptors (LXRs) and the farnesoid X receptors (FXRs) are activated by oxysterols and bile acids, respectively. Mounting evidence indicates that these nuclear receptors have essential roles, not only in the regulation of cholesterol and bile acid metabolism but also in the integration of sterol, fatty acid and glucose metabolism. PMID:22414897

  19. Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation

    SciTech Connect

    Bordbar, Aarash; Mo, Monica L.; Nakayasu, Ernesto S.; Rutledge, Alexandra C.; Kim, Young-Mo; Metz, Thomas O.; Jones, Marcus B.; Frank, Bryan C.; Smith, Richard D.; Peterson, Scott N.; Hyduke, Daniel R.; Adkins, Joshua N.; Palsson, Bernhard O.

    2012-06-26

    Macrophages are central players in the immune response, manifesting divergent phenotypes to control inflammation and innate immunity through the release of cytokines and other regulatory factor-dependent signaling pathways. In recent years, the focus on metabolism has been reemphasized as critical signaling and regulatory pathways of human pathophysiology, ranging from cancer to aging, often converge on metabolic responses. Here, we used genome-scale modeling and multi-omics (transcriptomics, proteomics, and metabolomics) analysis to assess metabolic features critical for macrophage functions. We constructed a genome-scale metabolic network for the RAW 264.7 cell line to determine metabolic modulators of macrophage activation. Metabolites well-known to be associated with immunoactivation (e.g., glucose and arginine) and immunosuppression (e.g., tryptophan and vitamin D3) were amongst the most critical effectors. Intracellular metabolic mechanisms linked to critical suppressive effectors were then assessed, identifying a suppressive role for de novo nucleotide synthesis. Finally, the underlying metabolic mechanisms of macrophage activation are identified by analyzing multi-omic data obtained from LPS-stimulated RAW cells in the context of our flux-based predictions. Our study demonstrates metabolism's role in regulating activation may be greater than previously anticipated and elucidates underlying metabolic connections between activation and metabolic effectors.

  20. Acclimation of aerobic-activated sludge degrading benzene derivatives and co-metabolic degradation activities of trichloroethylene by benzene derivative-grown aerobic sludge.

    PubMed

    Wang, Shizong; Yang, Qi; Bai, Zhiyong; Wang, Shidong; Wang, Yeyao; Nowak, Karolina M

    2015-01-01

    The acclimation of aerobic-activated sludge for degradation of benzene derivatives was investigated in batch experiments. Phenol, benzoic acid, toluene, aniline and chlorobenzene were concurrently added to five different bioreactors which contained the aerobic-activated sludge. After the acclimation process ended, the acclimated phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic-activated sludge were used to explore the co-metabolic degradation activities of trichloroethylene (TCE). Monod equation was employed to simulate the kinetics of co-metabolic degradation of TCE by benzene derivative-grown sludge. At the end of experiments, the mixed microbial communities grown under different conditions were identified. The results showed that the acclimation periods of microorganisms for different benzene derivatives varied. The maximum degradation rates of TCE for phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic sludge were 0.020, 0.017, 0.016, 0.0089 and 0.0047 mg g SS(-1) h(-1), respectively. The kinetic of TCE degradation in the absence of benzene derivative followed Monod equation well. Also, eight phyla were observed in the acclimated benzene derivative-grown aerobic sludge. Each of benzene derivative-grown aerobic sludge had different microbial community composition. This study can hopefully add new knowledge to the area of TCE co-metabolic by mixed microbial communities, and further the understanding on the function and applicability of aerobic-activated sludge.

  1. Estrogenic activity of diarylheptanoids from Curcuma comosa Roxb. Requires metabolic activation.

    PubMed

    Winuthayanon, Wipawee; Suksen, Kanoknetr; Boonchird, Chuenchit; Chuncharunee, Aporn; Ponglikitmongkol, Mathurose; Suksamrarn, Apichart; Piyachaturawat, Pawinee

    2009-02-11

    Curcuma comosa Roxb. has traditionally been used as a dietary supplement for health promotion in peri- and postmenopausal women in Thailand. We investigated the estrogenic activity of 7 naturally occurring diarylheptanoids from the extracts of C. comosa both in vitro and in vivo. A yeast recombinant system containing human estrogen receptor alpha, coactivator TIF2 and a beta-galactosidase reporter gene was used to determine estrogenic activity of diarylheptanoids metabolically activated with rat liver S9-fraction prior to the assay. The most potent compound was (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol, with a relative potency of 4% compared to 17beta-estradiol. The metabolic activation of diarylheptanoids markedly enhanced their efficiency. The chemical structure required for estrogenic activity of diarylheptanoids was the presence of a keto group at C3 and absence of hydroxyl moiety in ring B. Only diarylheptanoids showing full estrogenic efficiency in vitro were able to elicit uterotrophic activity of in immature ovariectomized rat. This is the first evidence for in vivo estrogenic activity of diarylheptanoids from C. comosa. This novel class of natural phytoestrogens has the potential to be developed for use as dietary supplement in the treatment of menopausal symptoms.

  2. Sustainable development of tyre char-based activated carbons with different textural properties for value-added applications.

    PubMed

    Hadi, Pejman; Yeung, Kit Ying; Guo, Jiaxin; Wang, Huaimin; McKay, Gordon

    2016-04-01

    This paper aims at the sustainable development of activated carbons for value-added applications from the waste tyre pyrolysis product, tyre char, in order to make pyrolysis economically favorable. Two activation process parameters, activation temperature (900, 925, 950 and 975 °C) and residence time (2, 4 and 6 h) with steam as the activating agent have been investigated. The textural properties of the produced tyre char activated carbons have been characterized by nitrogen adsorption-desorption experiments at -196 °C. The activation process has resulted in the production of mesoporous activated carbons confirmed by the existence of hysteresis loops in the N2 adsorption-desorption curves and the pore size distribution curves obtained from BJH method. The BET surface area, total pore volume and mesopore volume of the activated carbons from tyre char have been improved to 732 m(2)/g, 0.91 cm(3)/g and 0.89 cm(3)/g, respectively. It has been observed that the BET surface area, mesopore volume and total pore volume increased linearly with burnoff during activation in the range of experimental parameters studied. Thus, yield-normalized surface area, defined as the surface area of the activated carbon per gram of the precursor, has been introduced to optimize the activation conditions. Accordingly, the optimized activation conditions have been demonstrated as an activation temperature of 975 °C and an activation time of 4 h.

  3. Influence of host seed on metabolic activity by Enterobacter cloacae in the spermosphere

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known regarding the influences of nutrients released from plants on the metabolic activity of colonizing microbes. To gain a better understanding of these influences, we used bioluminescence- and oxygen consumption-based methods to compare bacterial metabolic activity expressed during col...

  4. Phenanthrene Metabolism in Smokers: Use of a Two-Step Diagnostic Plot Approach to Identify Subjects with Extensive Metabolic Activation

    PubMed Central

    Wang, Jing; Zhong, Yan; Carmella, Steven G.; Hochalter, J. Bradley; Rauch, Diane; Oliver, Andrew; Jensen, Joni; Hatsukami, Dorothy K.; Upadhyaya, Pramod; Hecht, Stephen S.

    2012-01-01

    Polycyclic aromatic hydrocarbons (PAHs) in cigarette smoke are among the most likely causes of lung cancer. PAHs require metabolic activation to initiate the carcinogenic process. Phenanthrene (Phe), a noncarcinogenic PAH, was used as a surrogate of benzo[α]pyrene and related PAHs to study the metabolic activation of PAHs in smokers. A dose of 10 μg of deuterated Phe ([D10]Phe) was administered to 25 healthy smokers in a crossover design, either as an oral solution or by smoking cigarettes containing [D10]Phe. Phe was deuterated to avoid interference from environmental Phe. Intensive blood and urine sampling was performed to quantitate the formation of deuterated r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene ([D10]PheT), a biomarker of the diol epoxide metabolic activation pathway. In both the oral and smoking arms approximately 6% of the dose was metabolically converted to diol epoxides, with a large intersubject variability in the formation of [D10]PheT observed. Two diagnostic plots were developed to identify subjects with large systemic exposure and significant lung contribution to metabolic activation. The combination of the two plots led to the identification of subjects with substantial local exposure. These subjects produced, in one single pass of [D10]Phe through the lung, a [D10]PheT exposure equivalent to the systemic exposure of a typical subject and may be an indicator of lung cancer susceptibility. Polymorphisms in PAH-metabolizing genes of the 25 subjects were also investigated. The integration of phenotyping and genotyping results indicated that GSTM1-null subjects produced approximately 2-fold more [D10]PheT than did GSTM1-positive subjects. PMID:22674470

  5. Laser light induced modulations in metabolic activities in human brain cancer

    NASA Astrophysics Data System (ADS)

    Tata, Darrell B.; Waynant, Ronald W.

    2008-03-01

    The role of low visible or near infra-red laser intensity in suppressing metabolic activity of malignant human brain cancer (glioblastoma) cells was investigated through the application of either a continuous wave 633nm HeNe or a pulsed picosecond 1,552nm wavelength laser. Human glioblastomas were exposed in their growth culture medium with serum for several energy doses. For both types of laser exposures the glioblastomas exhibited a maximal decline in the metabolic activity relative to their respective sham control counterparts at 10 J/cm2. The cellular metabolic activities for various treatment doses were measured through the colorimetric MTS metabolic assay after the laser exposure. Interestingly, addition of (the enzyme) catalase in the growth medium prior to the laser exposure was found to diminish the laser induced metabolic suppression for all fluence treatment conditions, thus suggesting a functional role of H IIO II in the metabolic suppression. Taken together, our findings reveal that visible or near infra-red low level light exposures could potentially be a viable tool in reducing the metabolic activity of cancers; evidence at hand implicates a role of light induced H IIO II in bringing about in part, suppression in the metabolic activity. Due to the cellular "biphasic" response to the laser exposure, further research needs to be undertaken to determine exposure parameters which would optimize metabolic and cellular growth suppression in-vivo.

  6. AMP-activated Protein Kinase Signaling Activation by Resveratrol Modulates Amyloid-β Peptide Metabolism*

    PubMed Central

    Vingtdeux, Valérie; Giliberto, Luca; Zhao, Haitian; Chandakkar, Pallavi; Wu, Qingli; Simon, James E.; Janle, Elsa M.; Lobo, Jessica; Ferruzzi, Mario G.; Davies, Peter; Marambaud, Philippe

    2010-01-01

    Alzheimer disease is an age-related neurodegenerative disorder characterized by amyloid-β (Aβ) peptide deposition into cerebral amyloid plaques. The natural polyphenol resveratrol promotes anti-aging pathways via the activation of several metabolic sensors, including the AMP-activated protein kinase (AMPK). Resveratrol also lowers Aβ levels in cell lines; however, the underlying mechanism responsible for this effect is largely unknown. Moreover, the bioavailability of resveratrol in the brain remains uncertain. Here we show that AMPK signaling controls Aβ metabolism and mediates the anti-amyloidogenic effect of resveratrol in non-neuronal and neuronal cells, including in mouse primary neurons. Resveratrol increased cytosolic calcium levels and promoted AMPK activation by the calcium/calmodulin-dependent protein kinase kinase-β. Direct pharmacological and genetic activation of AMPK lowered extracellular Aβ accumulation, whereas AMPK inhibition reduced the effect of resveratrol on Aβ levels. Furthermore, resveratrol inhibited the AMPK target mTOR (mammalian target of rapamycin) to trigger autophagy and lysosomal degradation of Aβ. Finally, orally administered resveratrol in mice was detected in the brain where it activated AMPK and reduced cerebral Aβ levels and deposition in the cortex. These data suggest that resveratrol and pharmacological activation of AMPK have therapeutic potential against Alzheimer disease. PMID:20080969

  7. Assessment of the activity of antiperspirants added to surgical hand disinfectants: methodological aspects and first observations.

    PubMed

    Pitten, F A; Rudolph, P; Below, H; Kramer, A

    2001-08-01

    Due to the risk of sensitization caused by glove powder, the use of unpowdered latex gloves is increasing. These unpowdered gloves need a special inner-surface layer which makes it easier for the applicant to put the glove on the hand and to remove it again. However, many users report difficulties with removing the gloves because of sweat production within the glove. Therefore, a method has been developed to evaluate the efficacy of antiperspirants which may be added either to the inner-surface layer of the glove or to hand disinfectants or to skin-care products used before the gloves are put on. The paper describes various trials to optimize this method.

  8. BAD-Dependent Regulation of Fuel Metabolism and KATP Channel Activity Confers Resistance to Epileptic Seizures

    PubMed Central

    Giménez-Cassina, Alfredo; Martínez-François, Juan Ramón; Fisher, Jill K.; Szlyk, Benjamin; Polak, Klaudia; Wiwczar, Jessica; Tanner, Geoffrey R.; Lutas, Andrew; Yellen, Gary; Danial, Nika N.

    2012-01-01

    Summary Neuronal excitation can be substantially modulated by alterations in metabolism, as evident from the anticonvulsant effect of diets that reduce glucose utilization and promote ketone body metabolism. We provide genetic evidence that BAD, a protein with dual functions in apoptosis and glucose metabolism, imparts reciprocal effects on metabolism of glucose and ketone bodies in brain cells. These effects involve phospho-regulation of BAD and are independent of its apoptotic function. BAD modifications that reduce glucose metabolism produce a marked increase in the activity of metabolically sensitive KATP channels in neurons, as well as resistance to behavioral and electrographic seizures in vivo. Seizure resistance is reversed by genetic ablation of the KATP channel, implicating the BAD-KATP axis in metabolic control of neuronal excitation and seizure responses. PMID:22632729

  9. Physical Activity and Sedentary Behavior Associated with Components of Metabolic Syndrome among People in Rural China

    PubMed Central

    Xiao, Jing; Shen, Chong; Chu, Min J.; Gao, Yue X.; Xu, Guang F.; Huang, Jian P.; Xu, Qiong Q.; Cai, Hui

    2016-01-01

    Background Metabolic syndrome is prevalent worldwide and its prevalence is related to physical activity, race, and lifestyle. Little data is available for people living in rural areas of China. In this study we examined associations of physical activity and sedentary behaviors with metabolic syndrome components among people in rural China. Methods The Nantong Metabolic Syndrome Study recruited 13,505 female and 6,997 male participants between 2007 and 2008. Data of socio-demographic characteristics and lifestyle were collected. The associations of physical activity and sedentary behaviors with metabolic syndrome components were analyzed. Results Prevalence of metabolic syndrome was 21.6%. It was significantly lower in men than in women. Low risks of metabolic syndrome were observed in those who did less sitting and engaged in more vigorous physical activity. The highest tertile of vigorous physical activity was associated with 15–40% decreased odds of metabolic syndrome and all of its components, except for low high-density lipoprotein cholesterol in men. Women with the highest tertile of moderate physical activity had 15–30% lower odds of central obesity, high glucose, and high triglycerides compared with those in the lowest tertile. Sitting time >42 hours per week had a 4%-12% attributable risk of metabolic syndrome, central obesity, and high triglycerides in both genders, and abnormal glucose and diastolic blood pressure in women. Sleeping for more than 8 hours per day was associated with risk of high serum glucose and lipids. Conclusions Our data suggested that physical activity has a preventive effect against metabolic syndrome and all its abnormal components, and that longer sitting time and sleep duration are associated with an increased risk of metabolic syndrome components, including central obesity and high triglycerides, glucose, and diastolic blood pressure. This study could provide information for future investigation into these associations. Also

  10. The mouse liver displays daily rhythms in the metabolism of phospholipids and in the activity of lipid synthesizing enzymes.

    PubMed

    Gorné, Lucas D; Acosta-Rodríguez, Victoria A; Pasquaré, Susana J; Salvador, Gabriela A; Giusto, Norma M; Guido, Mario Eduardo

    2015-02-01

    The circadian system involves central and peripheral oscillators regulating temporally biochemical processes including lipid metabolism; their disruption leads to severe metabolic diseases (obesity, diabetes, etc). Here, we investigated the temporal regulation of glycerophospholipid (GPL) synthesis in mouse liver, a well-known peripheral oscillator. Mice were synchronized to a 12:12 h light-dark (LD) cycle and then released to constant darkness with food ad libitum. Livers collected at different times exhibited a daily rhythmicity in some individual GPL content with highest levels during the subjective day. The activity of GPL-synthesizing/remodeling enzymes: phosphatidate phosphohydrolase 1 (PAP-1/lipin) and lysophospholipid acyltransferases (LPLATs) also displayed significant variations, with higher levels during the subjective day and at dusk. We evaluated the temporal regulation of expression and activity of phosphatidylcholine (PC) synthesizing enzymes. PC is mainly synthesized through the Kennedy pathway with Choline Kinase (ChoK) as a key regulatory enzyme or through the phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway. The PC/PE content ratio exhibited a daily variation with lowest levels at night, while ChoKα and PEMT mRNA expression displayed maximal levels at nocturnal phases. Our results demonstrate that mouse liver GPL metabolism oscillates rhythmically with a precise temporal control in the expression and/or activity of specific enzymes.

  11. Insect growth regulator activity of Cestrum parqui saponins: an interaction with cholesterol metabolism.

    PubMed

    Ikbal, C; Ben, Halima-Kamel M; Ben, Hamouda M H

    2006-01-01

    Cestrum parqui is an ornamental shrub known for its insecticidal activity against some insect pests; this activity comes from the crude saponic extract of the leaves of this plant, the saponins cause insect growth regulator symptoms (development and moulting perturbation). In this work we try to demonstrate the hypothesis that saponins interact with ecdysone (moulting hormone) synthesis mechanisms by reducing diet cholesterol absorption (cholesterol forms the skeleton of ecdysone and of other ecdysteroids). To show the cholesterol/saponin interaction we used a stored product pest insect (Tribolium confuisurn), the larva of this insect are affected by saponins added in their diet, but the addition of cholesterol permits to reduce significatively this insecticidal propriety. Using Spodoptera littoralis larva model the tentative to detect a cholesterol rate reduction on the level of hemolymph is also unsuccessful. All these experiments shows that this type of reaction can't occur in the diet or in the digestive system but probably in insect cells. It is clear that Cestrurn parqui saponins affect the cholesterol metabolism but the exactly mechanism is still unknown. More investigations are necessary to develop this hypothesis and to envisage the use of Cestrum saponins as insect growth regulator bioinsecticide.

  12. Extensive metabolic activation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in smokers

    PubMed Central

    Stepanov, Irina; Upadhyaya, Pramod; Carmella, Steven G.; Feuer, Rachel; Jensen, Joni; Hatsukami, Dorothy K.; Hecht, Stephen S.

    2008-01-01

    4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent lung carcinogen present in both unburned tobacco and cigarette smoke. The sum of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides, referred to as total NNAL, is an established urinary biomarker of human NNK uptake. Metabolic activation of NNK to DNA adducts proceeds via α-hydroxylation pathways, and 4-oxo-4-(3-pyridyl)butanoic acid (keto acid) and 4-hydroxy-4-(3-pyridyl)butanoic acid (hydroxy acid) are the principal end products of these pathways in rodents and primates. The purpose of this study was to determine NNK metabolic activation in smokers, as measured by the sum of keto acid and hydroxy acid, relative to total NNAL. To specifically identify NNK-derived keto acid and hydroxy acid, which are also formed extensively from nicotine, we added [pyridine-D4]NNK to cigarettes that were originally low in NNK, and measured the deuterium-labeled metabolites in the urine of people who smoked these cigarettes. The total amount of [pyridine-D4]keto acid plus [pyridine-D4]hydroxy acid averaged 4.00±2.49 nmol/24 h, while the average amount of total [pyridine-D4]NNAL was 0.511±0.368 nmol/24 h. The results of this study demonstrate for the first time that NNK metabolic activation is a quantitatively significant pathway in smokers, accounting for about 86% of total urinary excretion of NNK metabolites. The large interindividual variation in the excreted [pyridine-D4]keto acid and [pyridine-D4]hydroxy acid among 20 smokers strongly support our hypothesis that some smokers activate NNK more extensively than others, and that the ratio between biomarkers of metabolic activation and detoxification at a given dose of NNK could be a potential indicator of cancer risk. PMID:18628430

  13. Activation of CAR and PXR by Dietary, Environmental and Occupational Chemicals Alters Drug Metabolism, Intermediary Metabolism, and Cell Proliferation

    PubMed Central

    Hernandez, J.P.; Mota, L.C.; Baldwin, W.S.

    2010-01-01

    The constitutive androstane receptor (CAR) and the pregnane × receptor (PXR) are activated by a variety of endogenous and exogenous ligands, such as steroid hormones, bile acids, pharmaceuticals, and environmental, dietary, and occupational chemicals. In turn, they induce phase I–III detoxification enzymes and transporters that help eliminate these chemicals. Because many of the chemicals that activate CAR and PXR are environmentally-relevant (dietary and anthropogenic), studies need to address whether these chemicals or mixtures of these chemicals may increase the susceptibility to adverse drug interactions. In addition, CAR and PXR are involved in hepatic proliferation, intermediary metabolism, and protection from cholestasis. Therefore, activation of CAR and PXR may have a wide variety of implications for personalized medicine through physiological effects on metabolism and cell proliferation; some beneficial and others adverse. Identifying the chemicals that activate these promiscuous nuclear receptors and understanding how these chemicals may act in concert will help us predict adverse drug reactions (ADRs), predict cholestasis and steatosis, and regulate intermediary metabolism. This review summarizes the available data on CAR and PXR, including the environmental chemicals that activate these receptors, the genes they control, and the physiological processes that are perturbed or depend on CAR and PXR action. This knowledge contributes to a foundation that will be necessary to discern interindividual differences in the downstream biological pathways regulated by these key nuclear receptors. PMID:20871735

  14. Monocrotophos Induces the Expression and Activity of Xenobiotic Metabolizing Enzymes in Pre-Sensitized Cultured Human Brain Cells

    PubMed Central

    Tripathi, Vinay K.; Kumar, Vivek; Singh, Abhishek K.; Kashyap, Mahendra P.; Jahan, Sadaf; Pandey, Ankita; Alam, Sarfaraz; Khan, Feroz; Khanna, Vinay K.; Yadav, Sanjay; Lohani, Mohtshim; Pant, Aditya B.

    2014-01-01

    The expression and metabolic profile of cytochrome P450s (CYPs) is largely missing in human brain due to non-availability of brain tissue. We attempted to address the issue by using human brain neuronal (SH-SY5Y) and glial (U373-MG) cells. The expression and activity of CYP1A1, 2B6 and 2E1 were carried out in the cells exposed to CYP inducers viz., 3-methylcholanthrene (3-MC), cyclophosphamide (CPA), ethanol and known neurotoxicant- monocrotophos (MCP), a widely used organophosphorous pesticide. Both the cells show significant induction in the expression and CYP-specific activity against classical inducers and MCP. The induction level of CYPs was comparatively lower in MCP exposed cells than cells exposed to classical inducers. Pre-exposure (12 h) of cells to classical inducers significantly added the MCP induced CYPs expression and activity. The findings were concurrent with protein ligand docking studies, which show a significant modulatory capacity of MCP by strong interaction with CYP regulators-CAR, PXR and AHR. Similarly, the known CYP inducers- 3-MC, CPA and ethanol have also shown significantly high docking scores with all the three studied CYP regulators. The expression of CYPs in neuronal and glial cells has suggested their possible association with the endogenous physiology of the brain. The findings also suggest the xenobiotic metabolizing capabilities of these cells against MCP, if received a pre-sensitization to trigger the xenobiotic metabolizing machinery. MCP induced CYP-specific activity in neuronal cells could help in explaining its effect on neurotransmission, as these CYPs are known to involve in the synthesis/transport of the neurotransmitters. The induction of CYPs in glial cells is also of significance as these cells are thought to be involved in protecting the neurons from environmental insults and safeguard them from toxicity. The data provide better understanding of the metabolizing capability of the human brain cells against xenobiotics

  15. Renal metabolism and urinary excretion of platelet-activating factor in the rat

    SciTech Connect

    Noris, M.; Perico, N.; Macconi, D.; Nanni, V.; Dadan, J.; Peterlongo, F.; Remuzzi, G. )

    1990-11-15

    The origin of platelet-activating factor (PAF) in the urine remains ill defined. The present study documents that (3H)PAF (3.5 mu Ci) injected into the renal artery of isolated control rat kidney preparations perfused at constant pressure with a cell-free medium containing 1% bovine serum albumin (BSA) was excreted in negligible amounts (0.034%) in the urine, whereas 6% was retained by the kidney. When kidneys were perfused with a BSA-free medium, 0.029 and 71% of the total radioactivity added to the perfusate was recovered in the urine and in the renal tissue, respectively. (3H)PAF urine excretion in proteinuric kidneys from adriamycin-treated rats was still negligible (0.015%). Analysis of the renal tissue-retained radioactivity in control and proteinuric kidneys perfused with 1% BSA indicated metabolism into long chain acyl-sn-glycero-3-phosphorylcholine species, lyso-PAF, glycerols, and intact PAF. Thin layer chromatography analysis of (3H)glycerol fraction in these renal extracts showed two major components comigrating with 1-O-alkylglycerol and 1-O-alkyl-2-fatty acylglycerol. Isolated proximal tubules, but not glomeruli from nephrotic rats exposed to increasing concentrations of BSA (0-4%), had a higher PAF uptake than control tubules for BSA concentrations ranging from 0 to 0.1%. Our findings in the isolated perfused kidneys indicate that, in normal conditions, circulating PAF is excreted in the urine in negligible amounts and that the altered glomerular permeability to proteins does not affect this excretion rate. Moreover, analysis of renal tissue radioactivity documented that the renal metabolism of PAF is comparable in control and nephrotic kidneys.

  16. Promoted degradation of perfluorooctanic acid by persulfate when adding activated carbon.

    PubMed

    Lee, Yu-Chi; Lo, Shang-Lien; Kuo, Jeff; Huang, Chin-Pao

    2013-10-15

    Treatment of persistent perfluorooctanoic acid (PFOA) in water using persulfate (PS) oxidation typically requires an elevated temperature or UV irradiation, which is energy-consuming. Under relatively low temperatures of 25-45°C, activated carbon (AC) activated PS oxidation of PFOA was evaluated for its potential of practical applications. With presence of AC in PS oxidation, PFOA removal efficiency at 25°C reached 682% with a high defluorination efficiency of 549% after 12h and few intermediates of short-chain perfluorinated carboxylic acids (PFCAs) were found. The removal and defluorination rates with the combined AC/PS system were approximately 12 and 19 times higher than those of the PS-only system, respectively. Activated carbon not only removes PFOA through adsorption, but also activates PS to form sulfate radicals that accelerate the decomposition and mineralization of PFOA. The activation energy for PS oxidation of PFOA was reduced from 668 to 261kJ/mol by the catalytic effect of AC, which implies a lower reaction temperature and a shorter reaction time would suffice. A 2-cycle schematic reaction mechanism was used to describe PS oxidation of PFOA with the generation of various intermediates and end-products.

  17. Physical activity and metabolic risk among US youth: Mediation by obesity [abstract

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Physical activity has been inversely associated with metabolic risk, although pediatric studies are limited. It has been hypothesized that obesity mediates this relationship. Some studies reported that waist circumference (WC) is more highly related to metabolic risk than BMI, and may be a better me...

  18. Use of metabolic activation systems of tulip bulbs in the Ames test for environmental mutagens

    SciTech Connect

    Higashi, K.; Ikeuchi, K.; Karasaki, Y.

    1982-01-01

    The effects of trace amounts of PAH on the carcinogenesis in animals and human beings and on the ecology of plants are examined. An in vitro method has been developed which traces the metabolic fate of environmental mutagens in tulip bulbs. The method has been successful in confirming the presence of metabolic activation systems only for potent carcinogens. (JMT)

  19. Effects of petroleum on adrenocortical activity and on hepatic naphthalene-metabolizing activity in mallard ducks

    USGS Publications Warehouse

    Gorsline, J.; Holmes, W.N.

    1981-01-01

    Unstressed mallard ducks (Anas platyrhychos), given uncontaminated food and maintained on a short photoperiod, show two daily maxima in plasma corticosterone concentration ([B]); one occurring early in the light phase and a second just before the onset of darkness. After one week of exposure to food containing 3% (v/w) South Louisiana crude oil, plasma [B] were significantly lowered throughout the day. Similar abrupt declines in plasma [B] also occurred during the first 10 days of exposure to food containing 1% and 0.5% crude oil. Although the plasma [B] in birds consuming food contaminated with 0.5% crude oil increased between 10 and 50 days of exposure, the concentration after 50 days was still lower than normal. During the same interval, normal plasma [B] were restored in birds consuming food containing 1% and 3% crude oil. Significant increases occurred in the naphthalene-metabolizing properties of hepatic microsomes prepared from birds acutely exposed to all levels of petroleum-contaminated food and elevated levels were sustained throughout the first 50 days of exposure. Birds given food containing 3% crude oil for more than 50 days, however, showed steady declines in hepatic naphthalene-metabolizing activity. After 500 days, the activity was similar to that found in contemporaneous controls. During the same interval, the plasma [B] increased until the levels were higher than normal after 500 days of exposure; at this time, an inverse relationship, similar to that seen during the first week of exposure to contaminated food, was once more established between plasma [B] and the concomitant hepatic naphthalene-metabolizing activity.

  20. Active Thrusting Offshore Mount Lebanon: Source of the Tsunamigenic A.D. 551 Beirut-Tripoli Earthquake

    NASA Astrophysics Data System (ADS)

    Tapponnier, P.; Elias, A.; Singh, S.; King, G.; Briais, A.; Daeron, M.; Carton, H.; Sursock, A.; Jacques, E.; Jomaa, R.; Klinger, Y.

    2004-12-01

    On July 9, AD 551, a large earthquake, followed by a tsunami destroyed most of the coastal cities of Phoenicia (modern-day Lebanon). This was arguably one of the most devastating historical submarine earthquakes in the eastern Mediterranean. Geophysical data from the Shalimar survey unveils the source of this Mw=7.5 event: rupture of the offshore, hitherto unknown, 100?150 km-long, active, east-dipping Mount Lebanon Thrust (MLT). Deep-towed sonar swaths along the base of prominent bathymetric escarpments reveal fresh, west facing seismic scarps that cut the sediment-smoothed seafloor. The MLT trace comes closest (~ 8 km) to the coast between Beirut and Enfeh, where as 13 radiocarbon-calibrated ages indicate, a shoreline-fringing Vermetid bench suddenly emerged by ~ 80 cm in the 6th century AD. At Tabarja, the regular vertical separation (~ 1 m) of higher fossil benches, suggests uplift by 3 more comparable-size earthquakes since the Holocene sea-level reached a maximum ca. 7-6 ka, implying a 1500?1750 yr recurrence time. Unabated thrusting on the MLT likely orchestrated the growth of Mt. Lebanon since the late Miocene. The newly discovered MLT has been the missing piece in the Dead Sea Transform and eastern Mediterranean tectonic scheme. Identifying the source of the AD 551 event thus ends a complete reassessment of the sources of the major historical earthquakes on the various faults of the Lebanese Restraining Bend of the Levant Fault System (or Dead Sea Transform).

  1. Active Thrusting Offshore Mount Lebanon: Source of the Tsunamigenic A.D. 551 Beirut-Tripoli Earthquake

    NASA Astrophysics Data System (ADS)

    Tapponnier, P.; Elias, A.; Singh, S.; King, G.; Briais, A.; Daeron, M.; Carton, H.; Sursock, A.; Jacques, E.; Jomaa, R.; Klinger, Y.

    2007-12-01

    On July 9, AD 551, a large earthquake, followed by a tsunami destroyed most of the coastal cities of Phoenicia (modern-day Lebanon). This was arguably one of the most devastating historical submarine earthquakes in the eastern Mediterranean. Geophysical data from the Shalimar survey unveils the source of this Mw=7.5 event: rupture of the offshore, hitherto unknown, 100?150 km-long, active, east-dipping Mount Lebanon Thrust (MLT). Deep-towed sonar swaths along the base of prominent bathymetric escarpments reveal fresh, west facing seismic scarps that cut the sediment-smoothed seafloor. The MLT trace comes closest (~ 8 km) to the coast between Beirut and Enfeh, where as 13 radiocarbon-calibrated ages indicate, a shoreline-fringing Vermetid bench suddenly emerged by ~ 80 cm in the 6th century AD. At Tabarja, the regular vertical separation (~ 1 m) of higher fossil benches, suggests uplift by 3 more comparable-size earthquakes since the Holocene sea-level reached a maximum ca. 7-6 ka, implying a 1500?1750 yr recurrence time. Unabated thrusting on the MLT likely orchestrated the growth of Mt. Lebanon since the late Miocene. The newly discovered MLT has been the missing piece in the Dead Sea Transform and eastern Mediterranean tectonic scheme. Identifying the source of the AD 551 event thus ends a complete reassessment of the sources of the major historical earthquakes on the various faults of the Lebanese Restraining Bend of the Levant Fault System (or Dead Sea Transform).

  2. Seasonal metabolic changes in a year-round reproductively active subtropical tree-frog (Hypsiboas prasinus).

    PubMed

    Kiss, Ana Carolina I; de Carvalho, José Eduardo; Navas, Carlos A; Gomes, Fernando R

    2009-02-01

    Although seasonal metabolic variation in ectothermic tetrapods has been investigated primarily in the context of species showing some level of metabolic depression during winter, but several species of anurans maintain their activity patterns throughout the year in tropical and subtropical areas. The tree-frog Hypsiboas prasinus occurs in the subtropical Atlantic Forest and remains reproductively active during winter, at temperatures below 10 degrees C. We compared males calling in summer and winter, and found that males of H. prasinus exhibit seasonal adjustments in metabolic and morphometric variables. Individuals calling during winter were larger and showed higher resting metabolic rates than those calling during summer. Calling rates were not affected by season. Winter animals showed lower liver and heart activity level of citrate synthase (CS), partially compensated by larger liver mass. Winter individuals also showed higher activity of pyruvate kinase (PK) and lower activity of CS in trunk muscles, and higher activity of CS in leg muscles. Winter metabolic adjustments seem to be achieved by both compensatory mechanisms to the lower environmental temperature and a seasonally oriented aerobic depression of several organs. The impact of seasonal metabolic changes on calling performance and the capacity of subtropical anurans for metabolic thermal acclimatization are also discussed.

  3. Hairy AdS solitons

    NASA Astrophysics Data System (ADS)

    Anabalón, Andrés; Astefanesei, Dumitru; Choque, David

    2016-11-01

    We construct exact hairy AdS soliton solutions in Einstein-dilaton gravity theory. We examine their thermodynamic properties and discuss the role of these solutions for the existence of first order phase transitions for hairy black holes. The negative energy density associated to hairy AdS solitons can be interpreted as the Casimir energy that is generated in the dual filed theory when the fermions are antiperiodic on the compact coordinate.

  4. Chronology of Vesuvius' activity from A.D. 79 to 1631 based on archeomagnetism of lavas and historical sources

    NASA Astrophysics Data System (ADS)

    Principe, Claudia; Tanguy, Jean Claude; Arrighi, Simone; Paiotti, Anna; Goff, Maxime Le; Zoppi, Ugo

    2004-12-01

    The activity of Vesuvius between A.D. 79 and 1631 has been investigated by means of precise archaeomagnetic dating of primary volcanic deposits and taking into account the stratigraphy of lavas and tephra, historical written accounts, archaeological evidence related to the developing urbanisation, and radiocarbon ages. We found that the historical records are highly useful in constraining the timing of the main events, even if the data are often too scarce and imprecise for ascertaining the details of all phases of activity, especially their magnitude and emplacement of all the deposit types. In addition, some eruptions that took place in the 9th and 10th centuries appear to be unnoticed by historians. The archaeomagnetic study involved 26 sites of different lavas and 2 pyroclastic deposits. It shows that within the 15 centuries which elapsed between A.D. 79 and 1631, the effusive activity of Vesuvius clustered in the relatively short period of time between A.D. 787 and 1139 and was followed by a 5-century-long repose period. During this time Vesuvius prepared itself for the violent explosive eruption of 1631. The huge lavas shaping the morphology of the coast occurred largely through parasitic vents located outside the Mount Somma caldera. One of these parasitic vents is located at low elevation, very close to the densely inhabited town of Torre Annunziata. Among the various investigated lavas, a number of which were previously attributed to the 1631 eruption, none is actually younger than the 12th century. Therefore it is definitively concluded that the destructive 1631 event was exclusively explosive.

  5. In vivo osteogenic activity of bone marrow stromal stem cells transfected with Ad-GFP-hBMP-2.

    PubMed

    Wang, G X; Hu, L; Hu, H X; Zhang, Z; Liu, D P

    2014-06-16

    The aim of this study was to investigate the expression of bone morphogenetic protein-2 (BMP-2) in bone marrow stromal stem cells (BMSCs) and the in vivo and in vitro osteogenic activity of BMSCs transfected with the adenovirus plasmid, Ad-GFP-hBMP-2. The Ad-GFP-hBMP-2 plasmid was packaged and transfected into rabbit BMSCs to determine the transfection rate. The alkaline phosphatase (ALP) activities of Ad-GFP-hBMP-2-transfected BMSCs (experimental group) and untransfected BMSCs (control group) were detected. In situ hybridization of type I collagen and Western blot were used to determine the BMP-2 gene and protein expressions. The transfected and untransfected BMSCs were respectively inoculated into nude mice to observe in vivo osteogenesis. The decalcified bovine cancellous bone scaffold was respectively combined with transfected and untransfected BMSCs and implanted into ulnar defects in rabbits to repair the bone. The adenovirus titer was 1.2x10(10) pfu/mL. Green fluorescent protein expression appeared 48 h after transfection with the adenovirus plasmid, and the transfection rate was 71.1%. The ALP activity was higher in the experimental group than the control group at each time point after transfection. The gene and protein expressions of BMP-2 were higher in the experimental group than the control group. The positive rates of in vivo osteogenesis in the experimental and control groups were 90% and 40%, respectively. The bone defect repair effects differed markedly between the two groups. The BMP-2 gene can be highly expressed in BMSCs to successfully induce osteogenic differentiation. BMSCs can be used as seed cells for bone tissue engineering.

  6. Agmatine : metabolic pathway and spectrum of activity in brain.

    PubMed

    Halaris, Angelos; Plietz, John

    2007-01-01

    Agmatine is an endogenous neuromodulator that, based on animal studies, has the potential for new drug development. As an endogenous aminoguanidine compound (1-amino-4-guanidinobutane), it is structurally unique compared with other monoamines. Agmatine was long thought to be synthesised only in lower life forms, until its biosynthetic pathway (decarboxylation of arginine) was described in the mammalian brain in 1994. Human arginine decarboxylase has been cloned and shown to have 48% identity to ornithine decarboxylase. In neurons of the brain and spinal cord, agmatine is packaged into synaptic vesicles and released upon neuronal depolarisation. Other evidence of a neuromodulation role for agmatine is the presence of a specific cellular uptake mechanism and a specific metabolic enzyme (agmatinase; which forms putrescine).Initially, agmatine was conceptualised as an endogenous clonidine-displacing substance of imidazoline receptors; however, it has now been established to have affinity for several transmembrane receptors, such as alpha(2)-adrenergic, imidazoline I(1) and glutamatergic NMDA receptors. In addition to activity at these receptors, agmatine irreversibly inhibits neuronal nitric oxide synthase and downregulates inducible nitric oxide synthase. Endogenous agmatine is induced in response to stress and/or inflammation. Stressful conditions that induce agmatine include hypoxic-ischaemia and cold-restraint stress of ulcerogenic proportion. Induction of agmatine in the brain seems to occur in astrocytes, although neurons also synthesise agmatine. The effects of injected agmatine in animals include anticonvulsant-, antineurotoxic- and antidepressant-like actions. Intraperitoneal or intracerebroventricular injections of agmatine rapidly elicit antidepressant-like behavioural changes in the rodent forced swim test and tail suspension test. Intraperitoneal injections of agmatine into rats and mice also elicit acute anxiolytic-like behavioural changes in the elevated

  7. Improvements to the FATOLA computer program including added actively controlled landing gear subroutines

    NASA Technical Reports Server (NTRS)

    Mall, G. H.

    1983-01-01

    Modifications to a multi-degree-of-freedom flexible aircraft take-off and landing analysis (FATOLA) computer program, including a provision for actively controlled landing gears to expand the programs simulation capabilities, are presented. Supplemental instructions for preparation of data and for use of the modified program are included.

  8. Metabolic activities of five botryticides against Botrytis cinerea examined using the Biolog FF MicroPlate

    PubMed Central

    Wang, Hancheng; Wang, Jin; Li, Licui; Hsiang, Tom; Wang, Maosheng; Shang, Shenghua; Yu, Zhihe

    2016-01-01

    Tobacco grey mold caused by Botrytis cinerea is an important fungal disease worldwide. Boscalid, carbendazim, iprodione, pyrimethanil and propiconazole are representative botryticides for grey mold management. This research investigated the sensitivities of B. cinerea from tobacco to these chemicals using the Biolog FF Microplate. All five chemicals showed inhibitory activity, with average EC50 values of 0.94, 0.05, 0.50, 0.61 and 0.31 μg ml−1, respectively. B. cinerea metabolized 96.8% of tested carbon sources, including 29 effectively and 33 moderately, but the metabolic fingerprints differed under pressures imposed by these botryticides. For boscalid, B. cinerea was unable to metabolize many substrates related to tricarboxylic acid cycle. For carbendazim, carbon sources related to glycolysis were not metabolized. For iprodione, use of most carbon substrates was weakly inhibited, and the metabolic profile was similar to that of the control. For propiconazole, no carbon substrates were metabolized and the physiological and biochemical functions of the pathogen were totally inhibited. These findings provide useful information on metabolic activities of these botryticides, and may lead to future applications of the Biolog FF Microplate for examining metabolic effects of other fungicides on other fungi, as well as providing a metabolic fingerprint of B. cinerea that could be useful for identification. PMID:27491536

  9. Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome.

    PubMed

    Thorp, Alicia A; Schlaich, Markus P

    2015-01-01

    Sympathetic tone is well recognised as being implicit in cardiovascular control. It is less readily acknowledged that activation of the sympathetic nervous system is integral in energy homeostasis and can exert profound metabolic effects. Accumulating data from animal and human studies suggest that central sympathetic overactivity plays a pivotal role in the aetiology and complications of several metabolic conditions that can cluster to form the Metabolic Syndrome (MetS). Given the known augmented risk for type 2 diabetes, cardiovascular disease, and premature mortality associated with the MetS understanding the complex pathways underlying the metabolic derangements involved has become a priority. Many factors have been proposed to contribute to increased sympathetic nerve activity in metabolic abnormalities including obesity, impaired baroreflex sensitivity, hyperinsulinemia, and elevated adipokine levels. Furthermore there is mounting evidence to suggest that chronic sympathetic overactivity can potentiate two of the key metabolic alterations of the MetS, central obesity and insulin resistance. This review will discuss the regulatory role of the sympathetic nervous system in metabolic control and the proposed pathophysiology linking sympathetic overactivity to metabolic abnormalities. Pharmacological and device-based approaches that target central sympathetic drive will also be discussed as possible therapeutic options to improve metabolic control in at-risk patient cohorts.

  10. Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome

    PubMed Central

    Thorp, Alicia A.; Schlaich, Markus P.

    2015-01-01

    Sympathetic tone is well recognised as being implicit in cardiovascular control. It is less readily acknowledged that activation of the sympathetic nervous system is integral in energy homeostasis and can exert profound metabolic effects. Accumulating data from animal and human studies suggest that central sympathetic overactivity plays a pivotal role in the aetiology and complications of several metabolic conditions that can cluster to form the Metabolic Syndrome (MetS). Given the known augmented risk for type 2 diabetes, cardiovascular disease, and premature mortality associated with the MetS understanding the complex pathways underlying the metabolic derangements involved has become a priority. Many factors have been proposed to contribute to increased sympathetic nerve activity in metabolic abnormalities including obesity, impaired baroreflex sensitivity, hyperinsulinemia, and elevated adipokine levels. Furthermore there is mounting evidence to suggest that chronic sympathetic overactivity can potentiate two of the key metabolic alterations of the MetS, central obesity and insulin resistance. This review will discuss the regulatory role of the sympathetic nervous system in metabolic control and the proposed pathophysiology linking sympathetic overactivity to metabolic abnormalities. Pharmacological and device-based approaches that target central sympathetic drive will also be discussed as possible therapeutic options to improve metabolic control in at-risk patient cohorts. PMID:26064978

  11. Review of metabolic pathways activated in cancer cells as determined through isotopic labeling and network analysis.

    PubMed

    Dong, Wentao; Keibler, Mark A; Stephanopoulos, Gregory

    2017-02-10

    Cancer metabolism has emerged as an indispensable part of contemporary cancer research. During the past 10 years, the use of stable isotopic tracers and network analysis have unveiled a number of metabolic pathways activated in cancer cells. Here, we review such pathways along with the particular tracers and labeling observations that led to the discovery of their rewiring in cancer cells. The list of such pathways comprises the reductive metabolism of glutamine, altered glycolysis, serine and glycine metabolism, mutant isocitrate dehydrogenase (IDH) induced reprogramming and the onset of acetate metabolism. Additionally, we demonstrate the critical role of isotopic labeling and network analysis in identifying these pathways. The alterations described in this review do not constitute a complete list, and future research using these powerful tools is likely to discover other cancer-related pathways and new metabolic targets for cancer therapy.

  12. Quantifying interictal metabolic activity in human temporal lobe epilepsy

    SciTech Connect

    Henry, T.R.; Mazziotta, J.C.; Engel, J. Jr.; Christenson, P.D.; Zhang, J.X.; Phelps, M.E.; Kuhl, D.E. )

    1990-09-01

    The majority of patients with complex partial seizures of unilateral temporal lobe origin have interictal temporal hypometabolism on (18F)fluorodeoxyglucose positron emission tomography (FDG PET) studies. Often, this hypometabolism extends to ipsilateral extratemporal sites. The use of accurately quantified metabolic data has been limited by the absence of an equally reliable method of anatomical analysis of PET images. We developed a standardized method for visual placement of anatomically configured regions of interest on FDG PET studies, which is particularly adapted to the widespread, asymmetric, and often severe interictal metabolic alterations of temporal lobe epilepsy. This method was applied by a single investigator, who was blind to the identity of subjects, to 10 normal control and 25 interictal temporal lobe epilepsy studies. All subjects had normal brain anatomical volumes on structural neuroimaging studies. The results demonstrate ipsilateral thalamic and temporal lobe involvement in the interictal hypometabolism of unilateral temporal lobe epilepsy. Ipsilateral frontal, parietal, and basal ganglial metabolism is also reduced, although not as markedly as is temporal and thalamic metabolism.

  13. Characterization of phase I metabolism of resibufogenin and evaluation of the metabolic effects on its antitumor activity and toxicity.

    PubMed

    Ning, Jing; Yu, Zhen-Long; Hu, Liang-Hai; Wang, Chao; Huo, Xiao-Kui; Deng, Sa; Hou, Jie; Wu, Jing-Jing; Ge, Guang-Bo; Ma, Xiao-Chi; Yang, Ling

    2015-03-01

    Resibufogenin (RB), one of the major active compounds of the traditional Chinese medicine Chansu, has displayed great potential as a chemotherapeutic agent in oncology. However, it is a digoxin-like compound that also exhibits extremely cardiotoxic effects. The present study aimed to characterize the metabolic behaviors of RB in humans as well as to evaluate the metabolic effects on its bioactivity and toxicity. The phase I metabolic profile in human liver microsomes was characterized systemically, and the major metabolite was identified as marinobufagenin (5β-hydroxylresibufogenin, 5-HRB) by liquid chromatography-mass spectrometry and nuclear magnetic imaging techniques. Both cytochrome P450 (P450) reaction phenotyping and inhibition assays using P450-selective chemical inhibitors demonstrated that CYP3A4 was mainly involved in RB 5β-hydroxylation with much higher selectivity than CYP3A5. Kinetic characterization demonstrated that RB 5β-hydroxylation in both human liver microsomes and human recombinant CYP3A4 obeyed biphasic kinetics and displayed similar apparent kinetic parameters. Furthermore, 5-HRB could significantly induce cell growth inhibition and apoptosis in A549 and H1299 by facilitating apoptosome assembly and caspase activation. Meanwhile, 5-HRB displayed very weak cytotoxicity of human embryonic lung fibroblasts, and in mice there was a greater tolerance to acute toxicity. In summary, CYP3A4 dominantly mediated 5β-hydroxylation and was found to be a major metabolic pathway of RB in the human liver, whereas its major metabolite (5-HRB) displayed better druglikeness than its parent compound RB. Our findings lay a solid foundation for RB metabolism studies in humans and encourage further research on the bioactive metabolite of RB.

  14. Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

    PubMed

    Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

    2013-01-01

    Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities.

  15. Bovine liver slices combined with an androgen transcriptional activation assay: an in-vitro model to study the metabolism and bioactivity of steroids

    PubMed Central

    Wang, S.; Rijk, J. C. W.; Riethoff-Poortman, J. H.; Van Kuijk, S.; Peijnenburg, A. A. C. M.

    2010-01-01

    Previously we described the properties of a rapid and robust yeast androgen bioassay for detection of androgenic anabolic compounds, validated it, and showed its added value for several practical applications. However, biotransformation of potent steroids into inactive metabolites, or vice versa, is not included in this screening assay. Within this context, animal-friendly in-vitro cellular systems resembling species-specific metabolism can be of value. We therefore investigated the metabolic capacity of precision-cut slices of bovine liver using 17β-testosterone (T) as a model compound, because this is an established standard compound for assessing the metabolic capacity of such cellular systems. However, this is the first time that slice metabolism has been combined with bioactivity measurements. Moreover, this study also involves bioactivation of inactive prohormones, for example dehydroepiandrosterone (DHEA) and esters of T, and although medium extracts are normally analyzed by HPLC, here the metabolites formed were identified with more certainty by ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC–TOFMS) with accurate mass measurement. Metabolism of T resulted mainly in the formation of the less potent phase I metabolites 4-androstene-3,17-dione (4-AD), the hydroxy-T metabolites 6α, 6β, 15β, and 16α-OH-T, and the phase II metabolite T-glucuronide. As a consequence the overall androgenic activity, as determined by the yeast androgen bioassay, decreased. In order to address the usefulness of bovine liver slices for activation of inactive steroids, liver slices were exposed to DHEA and two esters of T. This resulted in an increase of androgenic activity, because of the formation of 4-AD and T. Figure Bovine liver slices for exposure studies in a 6-well format. PMID:20237917

  16. Metabolomics analysis of Cistus monspeliensis leaf extract on energy metabolism activation in human intestinal cells.

    PubMed

    Shimoda, Yoichi; Han, Junkyu; Kawada, Kiyokazu; Smaoui, Abderrazak; Isoda, Hiroko

    2012-01-01

    Energy metabolism is a very important process to improve and maintain health from the point of view of physiology. It is well known that the intracellular ATP production is contributed to energy metabolism in cells. Cistus monspeliensis is widely used as tea, spices, and medical herb; however, it has not been focusing on the activation of energy metabolism. In this study, C. monspeliensis was investigated as the food resources by activation of energy metabolism in human intestinal epithelial cells. C. monspeliensis extract showed high antioxidant ability. In addition, the promotion of metabolites of glycolysis and TCA cycle was induced by C. monspeliensis treatment. These results suggest that C. monspeliensis extract has an ability to enhance the energy metabolism in human intestinal cells.

  17. Metabolomics Analysis of Cistus monspeliensis Leaf Extract on Energy Metabolism Activation in Human Intestinal Cells

    PubMed Central

    Shimoda, Yoichi; Han, Junkyu; Kawada, Kiyokazu; Smaoui, Abderrazak; Isoda, Hiroko

    2012-01-01

    Energy metabolism is a very important process to improve and maintain health from the point of view of physiology. It is well known that the intracellular ATP production is contributed to energy metabolism in cells. Cistus monspeliensis is widely used as tea, spices, and medical herb; however, it has not been focusing on the activation of energy metabolism. In this study, C. monspeliensis was investigated as the food resources by activation of energy metabolism in human intestinal epithelial cells. C. monspeliensis extract showed high antioxidant ability. In addition, the promotion of metabolites of glycolysis and TCA cycle was induced by C. monspeliensis treatment. These results suggest that C. monspeliensis extract has an ability to enhance the energy metabolism in human intestinal cells. PMID:22523469

  18. Morphology transformation of Cu2O by adding TEOA and their antibacterial activity

    NASA Astrophysics Data System (ADS)

    Duan, Weijia; Zheng, Min; Li, Rong; Wang, Yuyuan

    2016-11-01

    Cu2O polyhedral particles and hollow spheres were successfully synthesized by adjusting the concentration of triethanolamine (TEOA). The as-prepared samples were structurally characterized by the scanning electron microscope (SEM), X-ray powder diffraction (XRD), and transmission electron microscopy (TEM). The results revealed that the solid polyhedral Cu2O with sizes ranging from 70 to 150 nm was in good crystallization. The diameter of the hollow Cu2O spheres increased to 350-450 nm. It was found that the sizes and morphologies of the products could be significantly affected by the concentration of TEOA. And the morphology of Cu2O transformed from solid polyhedrons to hollow spheres with the further enrichment of TEOA concentration. A possible mechanism was proposed to explain the formation of the hollow Cu2O spheres. In addition, we investigated the antibacterial activities of the samples. It was demonstrated that the hollow Cu2O sphere exhibited better antibacterial activities for Escherichia coli ( E. coli) and Staphylococcus aureus ( S. aureus) compared with the solid polyhedral Cu2O.

  19. Activity affects intraspecific body-size scaling of metabolic rate in ectothermic animals.

    PubMed

    Glazier, Douglas Stewart

    2009-10-01

    Metabolic rate is commonly thought to scale with body mass (M) to the 3/4 power. However, the metabolic scaling exponent (b) may vary with activity state, as has been shown chiefly for interspecific relationships. Here I use a meta-analysis of literature data to test whether b changes with activity level within species of ectothermic animals. Data for 19 species show that b is usually higher during active exercise (mean +/- 95% confidence limits = 0.918 +/- 0.038) than during rest (0.768 +/- 0.069). This significant upward shift in b to near 1 is consistent with the metabolic level boundaries hypothesis, which predicts that maximal metabolic rate during exercise should be chiefly influenced by volume-related muscular power production (scaling as M (1)). This dependence of b on activity level does not appear to be a simple temperature effect because body temperature in ectotherms changes very little during exercise.

  20. Drug activity screening based on microsomes-hydrogel system in predicting metabolism induced antitumor effect of oroxylin A

    PubMed Central

    Yang, Huiying; Li, Jianfeng; Zheng, Yuanting; Zhou, Lu; Tong, Shanshan; Zhao, Bei; Cai, Weimin

    2016-01-01

    A novel microsomes-hydrogel added cell culture system (MHCCS) was employed in the antitumor activity screening of natural compounds, aiming to achieve drug screening with better in vivo correlation, higher initiative to explore the potential active metabolites, and investigation of the antitumor mechanism from the perspective of metabolism. MTT assay and cell apoptosis detection showed that test drug oroxylin A (OA) had enhanced cytotoxicity and wogonin (W) with reduced cytotoxicity on MCF-7 cell line upon MHCCS incubation. In vivo antitumor evaluations also demonstrated that OA induced higher tumor inhibition than W at the same dosage. To explore the reasons, nine major metabolites of OA were separated and collected through UPLC-Q-TOF and semi-preparative HPLC. Metabolites M318 exhibited higher cytotoxicity than OA and other metabolites by MTT assay. 1H NMR spectrums, HPLC and TOF MS/MS results revealed that OA was catalyzed into its active metabolite M318 via a ring-opening reaction. M318 induced significant cell apoptosis and S-phase arrest through affecting tumor survival related genes after mechanism study. In conclusion, our MHCCS could be a useful tool for drug activity screening from a perspective of metabolism. PMID:26905263

  1. Substrate sources regulate spatial variation of metabolically active methanogens from two contrasting freshwater wetlands.

    PubMed

    Lin, Yongxin; Liu, Deyan; Ding, Weixin; Kang, Hojeong; Freeman, Chris; Yuan, Junji; Xiang, Jian

    2015-12-01

    There is ample evidence that methane (CH4) emissions from natural wetlands exhibit large spatial variations at a field scale. However, little is known about the metabolically active methanogens mediating these differences. We explored the spatial patterns in active methanogens of summer inundated Calamagrostis angustifolia marsh with low CH4 emissions and permanently inundated Carex lasiocarpa marsh with high CH4 emissions in Sanjiang Plain, China. In C. angustifolia marsh, the addition of (13)C-acetate significantly increased the CH4 production rate, and Methanosarcinaceae methanogens were found to participate in the consumption of acetate. In C. lasiocarpa marsh, there was no apparent increase in the CH4 production rate and no methanogen species were labeled with (13)C. When (13)CO2-H2 was added, however, CH4 production was found to be due to Fen Cluster (Methanomicrobiales) in C. angustifolia marsh and Methanobacterium Cluster B (Methanobacteriaceae) together with Fen Cluster in C. lasiocarpa marsh. These results suggested that CH4 was produced primarily by hydrogenotrophic methanogens using substrates mainly derived from plant litter in C. lasiocarpa marsh and by both hydrogenotrophic and acetoclastic methanogens using substrates mainly derived from root exudate in C. angustifolia marsh. The significantly lower CH4 emissions measured in situ in C. angustifolia marsh was primarily due to a deficiency of substrates compared to C. lasiocarpa marsh. Therefore, we speculate that the substrate source regulates both the type of active methanogens and the CH4 production pathway and consequently contributes to the spatial variations in CH4 productions observed in these freshwater marshes.

  2. Effects of petroleum contamination on soil microbial numbers, metabolic activity and urease activity.

    PubMed

    Guo, Huan; Yao, Jun; Cai, Minmin; Qian, Yiguang; Guo, Yue; Richnow, Hans H; Blake, Ruth E; Doni, Serena; Ceccanti, Brunello

    2012-06-01

    The influence of petroleum contamination on soil microbial activities was investigated in 13 soil samples from sites around an injection water well (Iw-1, 2, 3, 4) (total petroleum hydrocarbons (TPH): 7.5-78 mg kg(-1)), an oil production well (Op-1, 2, 3, 4, 5) (TPH: 149-1110 mg kg(-1)), and an oil spill accident well (Os-1, 2, 3, 4) (TPH: 4500-34600 mg kg(-1)). The growth rate constant (μ) of glucose stimulated organisms, determined by microcalorimetry, was higher in Iw soil samples than in Op and Os samples. Total cultivable bacteria and fungi and urease activity also decreased with increasing concentration of TPH. Total heat produced demonstrated that TPH at concentrations less than about 1 g kg(-1) soil stimulated anaerobic respiration. A positive correlation between TPH and soil organic matter (OM) and stimulation of fungi-bacteria-urease at low TPH doses suggested that TPH is bound to soil OM and slowly metabolized in Iw soils during OM consumption. These methods can be used to evaluate the potential of polluted soils to carry out self-bioremediation by metabolizing TPH.

  3. In vivo metabolic activity of hamster suprachiasmatic nuclei: use of anesthesia

    SciTech Connect

    Schwartz, W.J.

    1987-02-01

    In vivo glucose utilization was measured in the suprachiasmatic nuclei (SCN) of Golden hamsters using the /sup 14/C-labeled deoxyglucose technique. A circadian rhythm of SCN metabolic activity could be measured in this species, but only during pentobarbital sodium anesthesia when the surrounding background activity of adjacent hypothalamus was suppressed. Both the SCN's metabolic oscillation and its time-keeping ability are resistant to general anesthesia.

  4. Patterns of metabolic activity in the treatment of schizophrenia

    SciTech Connect

    Brodie, J.D.; Christman, D.R.; Corona, J.F.; Fowler, J.S.; Gomez-Mont, F.; Jaeger, J.; Micheels, P.A.; Rotrosen, J.; Russell, J.A.; Volkow, N.D.; Wikler, A.

    1984-04-01

    Six patients with chronic schizophrenia were studied with positron emission tomography (PET) before and after neuroleptic treatment, using fluorine-18-labeled fluorodeoxyglucose. After treatment, the mean whole-slice glucose metabolic rate at the level of the basal ganglia showed a 25% increase. However, patterns of frontal hypometabolism observed with the schizophrenic patients were not altered by medication. Pattern analysis using the fast Fourier transform was applied to a set of 422 images from a mixed group of normal, depressed, and schizophrenic subjects. Reconstruction of the images with low-frequency coefficients was excellent, reducing considerably the number of variables needed to characterize each image. Hierarchical cluster analysis categorized the transformed images according to anatomical level and subject group (patient versus control). The results suggest the utility of this procedure for the classification and characterization of metabolic PET images from psychiatric patients. 8 references, 3 figures, 1 table.

  5. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster

    PubMed Central

    Baenas, Nieves; Piegholdt, Stefanie; Schloesser, Anke; Moreno, Diego A.; García-Viguera, Cristina; Rimbach, Gerald; Wagner, Anika E.

    2016-01-01

    We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo), a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L) for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus. PMID:26901196

  6. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster.

    PubMed

    Baenas, Nieves; Piegholdt, Stefanie; Schloesser, Anke; Moreno, Diego A; García-Viguera, Cristina; Rimbach, Gerald; Wagner, Anika E

    2016-02-18

    We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo), a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L) for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus.

  7. Changes in phospholipid metabolism during B lymphocyte activation

    SciTech Connect

    Kriz, M.K.; Vitetta, E.S.; Sullivan, T.J.

    1986-07-15

    Phospholipid metabolism in murine B lymphocytes stimulated with anti-Ig bound to Sepharose has been examined. T cell-depleted splenic B lymphocytes cultured with Sepharose-coupled, affinity-purified goat anti-mouse Ig (GAMIg) increased the incorporation of /sup 32/PO/sub 4/ into phosphatidic acid and phosphatidylinositol within 3 hr and increased (/sup 3/H)-thymidine uptake at 48 hr. No increase in labeling was observed in phosphatidylethanolamine, phosphatidylcholine, or phosphatidylserine. Based on both negative and positive selection procedures, it was demonstrated that these responses occurred in B lymphocytes. In contrast to the thymidine uptake response did not require the presence of accessory cells or exogenous cytokines. The same selective changes in phospholipid metabolism were observed in neoplastic B lymphocytes (BCL/sub 1/) after treatment with Sepharose anti-..mu.., but not with Sepharose anti-Ia or Sepharose normal Ig. The dose-response relationships of /sup 32/PO/sub 4/ incorporation into phosphatidic acid and phosphatidylinositol and (/sup 3/H) thymidine uptake were nearly identical in BCL/sub 1/ cells. The results of these experiments indicate that interaction B lymphocytes with insolubilized anti-Ig results in prompt and selective changes in phospholipid metabolism that appear to be correlated with B lymphocyte proliferation.

  8. Bioorthogonal chemical imaging of metabolic activities in live mammalian hippocampal tissues with stimulated Raman scattering

    PubMed Central

    Hu, Fanghao; Lamprecht, Michael R.; Wei, Lu; Morrison, Barclay; Min, Wei

    2016-01-01

    Brain is an immensely complex system displaying dynamic and heterogeneous metabolic activities. Visualizing cellular metabolism of nucleic acids, proteins, and lipids in brain with chemical specificity has been a long-standing challenge. Recent development in metabolic labeling of small biomolecules allows the study of these metabolisms at the global level. However, these techniques generally require nonphysiological sample preparation for either destructive mass spectrometry imaging or secondary labeling with relatively bulky fluorescent labels. In this study, we have demonstrated bioorthogonal chemical imaging of DNA, RNA, protein and lipid metabolism in live rat brain hippocampal tissues by coupling stimulated Raman scattering microscopy with integrated deuterium and alkyne labeling. Heterogeneous metabolic incorporations for different molecular species and neurogenesis with newly-incorporated DNA were observed in the dentate gyrus of hippocampus at the single cell level. We further applied this platform to study metabolic responses to traumatic brain injury in hippocampal slice cultures, and observed marked upregulation of protein and lipid metabolism particularly in the hilus region of the hippocampus within days of mechanical injury. Thus, our method paves the way for the study of complex metabolic profiles in live brain tissue under both physiological and pathological conditions with single-cell resolution and minimal perturbation. PMID:28000773

  9. Bioorthogonal chemical imaging of metabolic activities in live mammalian hippocampal tissues with stimulated Raman scattering

    NASA Astrophysics Data System (ADS)

    Hu, Fanghao; Lamprecht, Michael R.; Wei, Lu; Morrison, Barclay; Min, Wei

    2016-12-01

    Brain is an immensely complex system displaying dynamic and heterogeneous metabolic activities. Visualizing cellular metabolism of nucleic acids, proteins, and lipids in brain with chemical specificity has been a long-standing challenge. Recent development in metabolic labeling of small biomolecules allows the study of these metabolisms at the global level. However, these techniques generally require nonphysiological sample preparation for either destructive mass spectrometry imaging or secondary labeling with relatively bulky fluorescent labels. In this study, we have demonstrated bioorthogonal chemical imaging of DNA, RNA, protein and lipid metabolism in live rat brain hippocampal tissues by coupling stimulated Raman scattering microscopy with integrated deuterium and alkyne labeling. Heterogeneous metabolic incorporations for different molecular species and neurogenesis with newly-incorporated DNA were observed in the dentate gyrus of hippocampus at the single cell level. We further applied this platform to study metabolic responses to traumatic brain injury in hippocampal slice cultures, and observed marked upregulation of protein and lipid metabolism particularly in the hilus region of the hippocampus within days of mechanical injury. Thus, our method paves the way for the study of complex metabolic profiles in live brain tissue under both physiological and pathological conditions with single-cell resolution and minimal perturbation.

  10. Bacterial community structure within an activated sludge reactor added with phenolic compounds.

    PubMed

    Gómez-Acata, Selene; Esquivel-Ríos, Ivonne; Pérez-Sandoval, Mariana Vivian; Navarro-Noya, Yendi; Rojas-Valdez, Aketzally; Thalasso, Frederic; Luna-Guido, Marco; Dendooven, Luc

    2016-12-16

    Biodegradation of phenolic compounds in bioreactors is well documented, but the changes in the bacterial populations dynamics during degradation were not that often. A glass bubble column used as reactor was inoculated with activated sludge, spiked with 2-chlorophenol, phenol and m-cresol after 28 days and maintained for an additional 56 days, while the 16S rRNA gene from metagenomic DNA was monitored. Proteobacteria (68.1%) dominated the inoculum, but the bacterial composition changed rapidly. The relative abundance of Bacteroidetes and Firmicutes decreased from 4.8 and 9.4 to <0.1 and 0.2% respectively, while that of Actinobacteria and TM7 increased from 4.8 and 2.0 to 19.2 and 16.1% respectively. Phenol application increased the relative abundance of Proteobacteria to 94.2% (mostly Brevundimonas 17.6%), while that of Bacteroidetes remained low (1.2%) until day 42. It then increased to 47.3% (mostly Leadbetterella 46.9%) at day 84. It was found that addition of phenolic compounds did not affect the relative abundance of the Alphaproteobacteria initially, but it decreased slowly while that of the Bacteroidetes increased towards the end.

  11. Age-related changes in core body temperature and activity in triple-transgenic Alzheimer's disease (3xTgAD) mice.

    PubMed

    Knight, Elysse M; Brown, Timothy M; Gümüsgöz, Sarah; Smith, Jennifer C M; Waters, Elizabeth J; Allan, Stuart M; Lawrence, Catherine B

    2013-01-01

    Alzheimer's disease (AD) is characterised, not only by cognitive deficits and neuropathological changes, but also by several non-cognitive behavioural symptoms that can lead to a poorer quality of life. Circadian disturbances in core body temperature and physical activity are reported in AD patients, although the cause and consequences of these changes are unknown. We therefore characterised circadian patterns of body temperature and activity in male triple transgenic AD mice (3xTgAD) and non-transgenic (Non-Tg) control mice by remote radiotelemetry. At 4 months of age, daily temperature rhythms were phase advanced and by 6 months of age an increase in mean core body temperature and amplitude of temperature rhythms were observed in 3xTgAD mice. No differences in daily activity rhythms were seen in 4- to 9-month-old 3xTgAD mice, but by 10 months of age an increase in mean daily activity and the amplitude of activity profiles for 3xTgAD mice were detected. At all ages (4-10 months), 3xTgAD mice exhibited greater food intake compared with Non-Tg mice. The changes in temperature did not appear to be solely due to increased food intake and were not cyclooxygenase dependent because the temperature rise was not abolished by chronic ibuprofen treatment. No β-amyloid (Aβ) plaques or neurofibrillary tangles were noted in the hypothalamus of 3xTgAD mice, a key area involved in temperature regulation, although these pathological features were observed in the hippocampus and amygdala of 3xTgAD mice from 10 months of age. These data demonstrate age-dependent changes in core body temperature and activity in 3xTgAD mice that are present before significant AD-related neuropathology and are analogous to those observed in AD patients. The 3xTgAD mouse might therefore be an appropriate model for studying the underlying mechanisms involved in non-cognitive behavioural changes in AD.

  12. Added Sugars

    MedlinePlus

    ... need sugar to function properly. Added sugars contribute zero nutrients but many added calories that can lead to extra pounds or even obesity, thereby reducing heart health. If you think of your daily calorie needs as a budget, you want to “spend” ...

  13. Value Added?

    ERIC Educational Resources Information Center

    UCLA IDEA, 2012

    2012-01-01

    Value added measures (VAM) uses changes in student test scores to determine how much "value" an individual teacher has "added" to student growth during the school year. Some policymakers, school districts, and educational advocates have applauded VAM as a straightforward measure of teacher effectiveness: the better a teacher,…

  14. Metabolic activity is necessary for activation of T suppressor cells by B cells

    SciTech Connect

    Elkins, K.L.; Stashak, P.W.; Baker, P.J. )

    1990-04-15

    Ag-primed B cells must express cell-surface IgM, but not IgD or Ia Ag, and must remain metabolically active, in order to activate suppressor T cells (Ts) specific for type III pneumococcal polysaccharide. Ag-primed B cells that were gamma-irradiated with 1000r, or less, retained the ability to activate Ts; however, Ag-primed B cells exposed to UV light were not able to do so. gamma-Irradiated and UV-treated Ag-primed B cells both expressed comparable levels of cell-surface IgM, and both localized to the spleen after in vivo transfer; neither could proliferate in vitro in response to mitogens. By contrast, gamma-irradiated primed B cells were still able to synthesize proteins, whereas UV-treated primed B cells could not. These findings suggest that in order for Ag-primed B cells to activate Ts, they must (a) express cell-associated IgM (sIgM) antibody bearing the idiotypic determinants of antibody specific for type III pneumococcal polysaccharide, and (b) be able to synthesize protein for either the continued expression of sIgM after cell transfer, or for the elaboration of another protein molecule that is also required for the activation of Ts; this molecule does not appear to be Ia Ag.

  15. Exposure of organic extracts of air particulates to sunlight leads to metabolic activation independence for mutagenicity.

    PubMed

    al-Khodairy, F; Hannan, M A

    1997-06-13

    Air particulates were collected on Whatman, GFA glass fibre filters using a RADECO constant-flow air sampler from a car-parking basement and an open roadside adjacent to the basement. While the basement was not exposed to sunlight, the roadside from where air samples were collected was exposed to regular daylight in the month of July (peak summer month). The filters were soaked and sonicated in acetone to dislodge the particulates and then a residue was obtained after evaporation of acetone. The residues were either held in dark or exposed to natural sunlight or germicidal UV light before being tested for mutagenicity using the Salmonella tester strain TA98 with and without metabolic activation (S9 mix). The results showed that the addition of S9 mix resulted in only a slight increase in the frequency of histidine revertants/plate in the case of daylight-exposed roadside air samples. On the other hand, a considerable increase in mutagenicity was observed in the case of the basement air samples, particularly at higher concentrations of the organic extracts when S9 mix was added. However, a pre-exposure of the organic extract of air from the basement to sunlight abrogated the need for S9 mix for showing mutagenic activity. A pre-exposure of the same extracts to germicidal UV light failed to produce a similar effect. These results suggested that long wavelengths of natural sunlight could be responsible for the conversion of certain promutagens in air particulates into direct-acting mutagens. The environmental impact of solar radiation as a modifier of air particulate mutagens in high-sun countries like Saudi Arabia needs to be carefully considered for assessment of air pollution-related health risks.

  16. Human Neural Stem Cell Transplantation Rescues Cognitive Defects in APP/PS1 Model of Alzheimer’s Disease by Enhancing Neuronal Connectivity and Metabolic Activity

    PubMed Central

    Li, Xueyuan; Zhu, Hua; Sun, Xicai; Zuo, Fuxing; Lei, Jianfeng; Wang, Zhanjing; Bao, Xinjie; Wang, Renzhi

    2016-01-01

    Alzheimer’s disease (AD), the most frequent type of dementia, is featured by Aβ pathology, neural degeneration and cognitive decline. To date, there is no cure for this disease. Neural stem cell (NSC) transplantation provides new promise for treating AD. Many studies report that intra-hippocampal transplantation of murine NSCs improved cognition in rodents with AD by alleviating neurodegeneration via neuronal complement or replacement. However, few reports examined the potential of human NSC transplantation for AD. In this study, we implanted human brain-derived NSCs (hNSCs) into bilateral hippocampus of an amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic (Tg) mouse model of AD to test the effects of hNSC transplantation on Alzheimer’s behavior and neuropathology. Six weeks later, transplanted hNSCs engrafted into the brains of AD mice, migrated dispersedly in broad brain regions, and some of them differentiated into neural cell types of central nervous system (CNS). The hNSC transplantation restored the recognition, learning and memory deficits but not anxiety tasks in AD mice. Although Aβ plaques were not significantly reduced, the neuronal, synaptic and nerve fiber density was significantly increased in the frontal cortex and hippocampus of hNSC-treated AD mice, suggesting of improved neuronal connectivity in AD brains after hNSC transplantation. Ultrastructural analysis confirmed that synapses and nerve fibers maintained relatively well-structured shapes in these mice. Furthermore, in vivo magnetic resonance spectroscopy (MRS) showed that hNSC-treated mice had notably increased levels of N-acetylaspartate (NAA) and Glu in the frontal cortex and hippocampus, suggesting that neuronal metabolic activity was improved in AD brains after hNSC transplantation. These results suggest that transplanted hNSCs rescued Alzheimer’s cognition by enhancing neuronal connectivity and metabolic activity through a compensation mechanism in APP/PS1 mice. This

  17. An increase in minimum metabolic rate and not activity explains field metabolic rate changes in a breeding seabird.

    PubMed

    Green, J A; Aitken-Simpson, E J; White, C R; Bunce, A; Butler, P J; Frappell, P B

    2013-05-01

    The field metabolic rate (FMR) of a free-ranging animal can be considered as the sum of its maintenance costs (minimum metabolic rate, MMR) and additional costs associated with thermoregulation, digestion, production and activity. However, the relationships between FMR and BMR and how they relate to behaviour and extrinsic influences is not clear. In seabirds, FMR has been shown to increase during the breeding season. This is presumed to be the result of an increase in foraging activity, stimulated by increased food demands from growing chicks, but few studies have investigated in detail the factors that underlie these increases. We studied free-ranging Australasian gannets (Morus serrator) throughout their 5 month breeding season, and evaluated FMR, MMR and activity-related metabolic costs on a daily basis using the heart rate method. In addition, we simultaneously recorded behaviour (flying and diving) in the same individuals. FMR increased steadily throughout the breeding season, increasing by 11% from the incubation period to the long chick-brooding period. However, this was not accompanied by either an increase in flying or diving behaviour, or an increase in the energetic costs of activity. Instead, the changes in FMR could be explained exclusively by a progressive increase in MMR. Seasonal changes in MMR could be due to a change in body composition or a decrease in body condition associated with changing the allocation of resources between provisioning adults and growing chicks. Our study highlights the importance of measuring physiological parameters continuously in free-ranging animals in order to understand fully the mechanisms underpinning seasonal changes in physiology and behaviour.

  18. Control of YAP/TAZ Activity by Metabolic and Nutrient-Sensing Pathways.

    PubMed

    Santinon, Giulia; Pocaterra, Arianna; Dupont, Sirio

    2016-04-01

    Metabolism is a fundamental cellular function that can be reprogrammed by signaling pathways and oncogenes to meet cellular requirements. An emerging paradigm is that signaling and transcriptional networks can be in turn regulated by metabolism, allowing cells to coordinate their metabolism and behavior in an integrated manner. The activity of the YAP/TAZ transcriptional coactivators, downstream transducers of the Hippo cascade and powerful pro-oncogenic factors, was recently found to be regulated by metabolic pathways, such as aerobic glycolysis and mevalonate synthesis, and by the nutrient-sensing LKB1-AMPK and TSC-mTOR pathways. We discuss here current data linking YAP/TAZ to metabolism and suggest how this coupling might coordinate nutrient availability with genetic programs that sustain tissue growth, neoplastic cell proliferation, and tumor malignancy.

  19. Temporal repeatability of metabolic rate and the effect of organ mass and enzyme activity on metabolism in European eel (Anguilla anguilla).

    PubMed

    Boldsen, Martin Maagaard; Norin, Tommy; Malte, Hans

    2013-05-01

    Intraspecific variation in metabolic rate of fish can be pronounced and have been linked to various fitness-related behavioural and physiological traits, but the underlying causes for this variation have received far less attention than the consequences of it. In the present study we investigated whether European eels (Anguilla anguilla) displayed temporal repeatability of body-mass-corrected (residual) metabolic rate over a two-month period and if variations in organ mass and enzyme activity between individual fish could be the cause for the observed variation in metabolic rate. Both standard metabolic rate (SMR; Pearson's r=0.743) and routine metabolic rate (RMR; r=0.496) were repeatable over the two-month period. Repeatability of RMR is an interesting finding as it indicates that the level of spontaneous activity in respirometer-confined fish is not random. Cumulative organ mass (liver, heart, spleen and intestine; mean 1.6% total body mass) was found to explain 38% of the variation in SMR (r=0.613) with the liver (one of the metabolically most active organs) being the driver for the correlation between organ mass and metabolic rate. No relationships were found for either liver citrate synthase or cytochrome oxidase activity and metabolic rate in the European eels. Reasons for, and contributions to, the observed variation in metabolic rate are discussed.

  20. Polyphosphate - an ancient energy source and active metabolic regulator

    PubMed Central

    2011-01-01

    There are a several molecules on Earth that effectively store energy within their covalent bonds, and one of these energy-rich molecules is polyphosphate. In microbial cells, polyphosphate granules are synthesised for both energy and phosphate storage and are degraded to produce nucleotide triphosphate or phosphate. Energy released from these energetic carriers is used by the cell for production of all vital molecules such as amino acids, nucleobases, sugars and lipids. Polyphosphate chains directly regulate some processes in the cell and are used as phosphate donors in gene regulation. These two processes, energetic metabolism and regulation, are orchestrated by polyphosphate kinases. Polyphosphate kinases (PPKs) can currently be categorized into three groups (PPK1, PPK2 and PPK3) according their functionality; they can also be divided into three groups according their homology (EcPPK1, PaPPK2 and ScVTC). This review discusses historical information, similarities and differences, biochemical characteristics, roles in stress response regulation and possible applications in the biotechnology industry of these enzymes. At the end of the review, a hypothesis is discussed in view of synthetic biology applications that states polyphosphate and calcium-rich organelles have endosymbiotic origins from ancient protocells that metabolized polyphosphate. PMID:21816086

  1. Differences in activities of the enzymes of nucleotide metabolism and its implications for cardiac xenotransplantation.

    PubMed

    Yuen, A H Y; Khalpey, Z; Lavitrano, M; McGregor, C G A; Kalsi, K K; Yacoub, M H; Smolenski, R T

    2006-01-01

    Xenotransplantation is one be possible solution for a severe shortage of human organs available for transplantation. However, only a few studies addressed metabolic compatibility of transplanted animal organs. Our aim was to compare activities of adenosine metabolizing enzymes in the heart of different species that are relevant to clinical or experimental xenotransplantation. We noted fundamental differences: ecto-5' nucleotidease (E5' N) activity was 4-fold lower in pig and baboon hearts compared to the human hearts while mouse activity was compatible with human and rat activity was three times higher than human. There also were significant differences in AMP-deaminase (AMPD), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities. We conclude that differences in nucleotide metabolism may contribute to organ dysfunction after xenotransplantation.

  2. Low Levels of Physical Activity Increase Metabolic Responsiveness to Cold in a Rat (Rattus fuscipes)

    PubMed Central

    Seebacher, Frank; Glanville, Elsa J.

    2010-01-01

    Background Physical activity modulates expression of metabolic genes and may therefore be a prerequisite for metabolic responses to environmental stimuli. However, the extent to which exercise interacts with environmental conditions to modulate metabolism is unresolved. Hence, we tested the hypothesis that even low levels of physical activity are beneficial by improving metabolic responsiveness to temperatures below the thermal neutral zone, thereby increasing the capacity for substrate oxidation and energy expenditure. Methodology/Principal Findings We used wild rats (Rattus fuscipes) to avoid potential effects of breeding on physiological phenotypes. Exercise acclimation (for 30 min/day on 5 days/week for 30 days at 60% of maximal performance) at 22°C increased mRNA concentrations of PGC1α, PPARδ, and NRF-1 in skeletal muscle and brown adipose tissue compared to sedentary animals. Lowering ambient temperature to 12°C caused further increases in relative expression of NRF-1 in skeletal muscle, and of PPARδ of brown adipose tissue. Surprisingly, relative expression of UCP1 increased only when both exercise and cold stimuli were present. Importantly, in sedentary animals cold acclimation (12°C) alone did not change any of the above variables. Similarly, cold alone did not increase maximum capacity for substrate oxidation in mitochondria (cytochrome c oxidase and citrate synthase activities) of either muscle or brown adipose tissue. Animals that exercised regularly had higher exercise induced metabolic rates in colder environments than sedentary rats, and temperature induced metabolic scope was greater in exercised rats. Conclusions/Significance Physical activity is a necessary prerequisite for the expression of transcriptional regulators that influence a broad range of physiological functions from energy metabolism to cardiovascular function and nutrient uptake. A sedentary lifestyle leads to decreased daily energy expenditure because of a lack of direct use

  3. Activities of xenobiotic metabolizing enzymes in rat placenta and liver in vitro.

    PubMed

    Fabian, Eric; Wang, Xinyi; Engel, Franziska; Li, Hequn; Landsiedel, Robert; van Ravenzwaay, Bennard

    2016-06-01

    In order to assess whether the placental metabolism of xenobiotic compounds should be taken into consideration for physiologically-based toxicokinetic (PBTK) modelling, the activities of seven phase I and phase II enzymes have been quantified in the 18-day placenta of untreated Wistar rats. To determine their relative contribution, these activities were compared to those of untreated adult male rat liver, using commonly accepted assays. The enzymes comprised cytochrome P450 (CYP), flavin-containing monooxygenase (FMO), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), esterase, UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST). In contrast to liver, no activities were measurable for 7-ethylresorufin-O-dealkylase (CYP1A), 7-pentylresorufin-O-dealkylase (CYP2B), 7-benzylresorufin-O-dealkylase (CYP2B, 2C and 3 A), UGT1, UGT2 and GST in placenta, indicating that the placental activity of these enzymes was well below their hepatic activity. Low activities in placenta were determined for FMO (4%), and esterase (8%), whereas the activity of placental ADH and ALDH accounted for 35% and 40% of the hepatic activities, respectively. In support of the negligible placental CYP activity, testosterone and six model azole fungicides, which were readily metabolized by rat hepatic microsomes, failed to exhibit any metabolic turnover with rat placental microsomes. Hence, with the possible exception of ADH and ALDH, the activities of xenobiotic-metabolizing enzymes in rat placenta are too low to warrant consideration in PBTK modelling.

  4. Peroxisome Proliferator-Activated Receptor Targets for the Treatment of Metabolic Diseases

    PubMed Central

    Monsalve, Francisco A.; Pyarasani, Radha D.; Delgado-Lopez, Fernando; Moore-Carrasco, Rodrigo

    2013-01-01

    Metabolic syndrome is estimated to affect more than one in five adults, and its prevalence is growing in the adult and pediatric populations. The most widely recognized metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a proinflammatory state as well. Peroxisome proliferator-activated receptors (PPARs) may serve as potential therapeutic targets for treating the metabolic syndrome and its related risk factors. The PPARs are transcriptional factors belonging to the ligand-activated nuclear receptor superfamily. So far, three isoforms of PPARs have been identified, namely, PPAR-α, PPAR-β/δ, and PPAR-γ. Various endogenous and exogenous ligands of PPARs have been identified. PPAR-α and PPAR-γ are mainly involved in regulating lipid metabolism, insulin sensitivity, and glucose homeostasis, and their agonists are used in the treatment of hyperlipidemia and T2DM. Whereas PPAR-β/δ function is to regulate lipid metabolism, glucose homeostasis, anti-inflammation, and fatty acid oxidation and its agonists are used in the treatment of metabolic syndrome and cardiovascular diseases. This review mainly focuses on the biological role of PPARs in gene regulation and metabolic diseases, with particular focus on the therapeutic potential of PPAR modulators in the treatment of thrombosis. PMID:23781121

  5. Metabolic syndrome remodels electrical activity of the sinoatrial node and produces arrhythmias in rats.

    PubMed

    Albarado-Ibañez, Alondra; Avelino-Cruz, José Everardo; Velasco, Myrian; Torres-Jácome, Julián; Hiriart, Marcia

    2013-01-01

    In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias. The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node. We observed that in the sinoatrial node of "metabolic syndrome rats", compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats. We conclude that metabolic syndrome produces a dysfunction SA node by disrupting normal architecture and the electrical activity, which could explain the onset of arrhythmias in rats.

  6. How Effective Are Active Videogames Among the Young and the Old? Adding Meta-analyses to Two Recent Systematic Reviews

    PubMed Central

    Crutzen, Rik; Lu, Amy Shirong

    2014-01-01

    Abstract Objective: Two recent systematic reviews have surveyed the existing evidence for the effectiveness of active videogames in children/adolescents and in elderly people. In the present study, effect sizes were added to these systematic reviews, and meta-analyses were performed. Materials and Methods: All reviewed studies were considered for inclusion in the meta-analyses, but only studies were included that investigated the effectiveness of active videogames, used an experimental design, and used actual health outcomes as the outcome measures (body mass index for children/adolescents [k=5] and functional balance for the elderly [k=6]). Results: The average effect of active videogames in children and adolescents was small and nonsignificant: Hedges' g=0.20 (95 percent confidence interval, −0.08 to 0.48). Limited heterogeneity was observed, and no moderator analyses were performed. For the effect of active videogames on functional balance in the elderly, the analyses revealed a medium-sized and significant effect of g=0.68 (95 percent confidence interval, 0.13–1.24). For the elderly studies, substantial heterogeneity was observed. Moderator analyses showed that there were no significant effects of using a no-treatment control group versus an alternative treatment control group or of using games that were especially created for health-promotion purposes versus off-the-shelf games. Also, intervention duration and frequency, sample size, study quality, and dropout did not significantly moderate the effect of active videogames. Conclusions: The results of these meta-analyses provide preliminary evidence that active videogames can have positive effects on relevant outcome measures in children/adolescents and elderly individuals. PMID:26192486

  7. Metaproteomics: extracting and mining proteome information to characterize metabolic activities in microbial communities.

    PubMed

    Abraham, Paul E; Giannone, Richard J; Xiong, Weili; Hettich, Robert L

    2014-06-17

    Contemporary microbial ecology studies usually employ one or more "omics" approaches to investigate the structure and function of microbial communities. Among these, metaproteomics aims to characterize the metabolic activities of the microbial membership, providing a direct link between the genetic potential and functional metabolism. The successful deployment of metaproteomics research depends on the integration of high-quality experimental and bioinformatic techniques for uncovering the metabolic activities of a microbial community in a way that is complementary to other "meta-omic" approaches. The essential, quality-defining informatics steps in metaproteomics investigations are: (1) construction of the metagenome, (2) functional annotation of predicted protein-coding genes, (3) protein database searching, (4) protein inference, and (5) extraction of metabolic information. In this article, we provide an overview of current bioinformatic approaches and software implementations in metaproteome studies in order to highlight the key considerations needed for successful implementation of this powerful community-biology tool.

  8. Whole-organism screening for gluconeogenesis identifies activators of fasting metabolism

    PubMed Central

    Gut, Philipp; Baeza-Raja, Bernat; Andersson, Olov; Hasenkamp, Laura; Hsiao, Joseph; Hesselson, Daniel; Akassoglou, Katerina; Verdin, Eric; Hirschey, Matthew D.; Stainier, Didier Y.R.

    2012-01-01

    Improving the control of energy homeostasis can lower cardiovascular risk in metabolically compromised individuals. To identify new regulators of whole-body energy control, we conducted a high-throughput screen in transgenic reporter zebrafish for small molecules that modulate the expression of the fasting-inducible gluconeogenic gene pck1. We show that this in vivo strategy identified several drugs that impact gluconeogenesis in humans, as well as metabolically uncharacterized compounds. Most notably, we find that the Translocator Protein (TSPO) ligands PK 11195 and Ro5-4864 are glucose lowering agents despite a strong inductive effect on pck1 expression. We show that these drugs are activators of a fasting-like energy state, and importantly that they protect high-fat diet induced obese mice from hepatosteatosis and glucose intolerance, two pathological manifestations of metabolic dysregulation. Thus, using a whole-organism screening strategy, this study has identified new small molecule activators of fasting metabolism. PMID:23201900

  9. Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies

    PubMed Central

    Heikal, Ahmed A

    2010-01-01

    Mitochondria play a pivotal role in energy metabolism, programmed cell death and oxidative stress. Mutated mitochondrial DNA in diseased cells compromises the structure of key enzyme complexes and, therefore, mitochondrial function, which leads to a myriad of health-related conditions such as cancer, neurodegenerative diseases, diabetes and aging. Early detection of mitochondrial and metabolic anomalies is an essential step towards effective diagnoses and therapeutic intervention. Reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) play important roles in a wide range of cellular oxidation–reduction reactions. Importantly, NADH and FAD are naturally fluorescent, which allows noninvasive imaging of metabolic activities of living cells and tissues. Furthermore, NADH and FAD autofluorescence, which can be excited using distinct wavelengths for complementary imaging methods and is sensitive to protein binding and local environment. This article highlights recent developments concerning intracellular NADH and FAD as potential biomarkers for metabolic and mitochondrial activities. PMID:20406068

  10. Metaproteomics: extracting and mining proteome information to characterize metabolic activities in microbial communities

    SciTech Connect

    Abraham, Paul E; Giannone, Richard J; Xiong, Weili; Hettich, Robert {Bob} L

    2014-01-01

    Contemporary microbial ecology studies usually employ one or more omics approaches to investigate the structure and function of microbial communities. Among these, metaproteomics aims to characterize the metabolic activities of the microbial membership, providing a direct link between the genetic potential and functional metabolism. The successful deployment of metaproteomics research depends on the integration of high-quality experimental and bioinformatic techniques for uncovering the metabolic activities of a microbial community in a way that is complementary to other meta-omic approaches. The essential, quality-defining informatics steps in metaproteomics investigations are: (1) construction of the metagenome, (2) functional annotation of predicted protein-coding genes, (3) protein database searching, (4) protein inference, and (5) extraction of metabolic information. In this article, we provide an overview of current bioinformatic approaches and software implementations in metaproteome studies in order to highlight the key considerations needed for successful implementation of this powerful community-biology tool.

  11. Metabolic syndrome: adenosine monophosphate-activated protein kinase and malonyl coenzyme A.

    PubMed

    Ruderman, Neil B; Saha, Asish K

    2006-02-01

    The metabolic syndrome can be defined as a state of metabolic dysregulation characterized by insulin resistance, central obesity, and a predisposition to type 2 diabetes, dyslipidemia, premature atherosclerosis, and other diseases. An increasing body of evidence has linked the metabolic syndrome to abnormalities in lipid metabolism that ultimately lead to cellular dysfunction. We review here the hypothesis that, in many instances, the cause of these lipid abnormalities could be a dysregulation of the adenosine monophosphate-activated protein kinase (AMPK)/malonyl coenzyme A (CoA) fuel-sensing and signaling mechanism. Such dysregulation could be reflected by isolated increases in malonyl CoA or by concurrent changes in malonyl CoA and AMPK, both of which would alter intracellular fatty acid partitioning. The possibility is also raised that pharmacological agents and other factors that activate AMPK and/or decrease malonyl CoA could be therapeutic targets.

  12. A microfluidic device for evaluating the dynamics of the metabolism-dependent antioxidant activity of nutrients.

    PubMed

    Lee, Jungwoo; Choi, Jong-ryul; Ha, Sang Keun; Choi, Inwook; Lee, Seung Hwan; Kim, Donghyun; Choi, Nakwon; Sung, Jong Hwan

    2014-08-21

    Various food components are known for their health-promoting effects. However, their biochemical effects are generally evaluated in vitro, and their actual in vivo effect can vary significantly, depending on their metabolic profiles. To evaluate the effect of the liver metabolism on the antioxidant activity, we have developed a two-compartment microfluidic system that integrates the dynamics of liver metabolism and the subsequent antioxidant activity of food components. In the first compartment of the device, human liver enzyme fractions were immobilized inside a poly(ethylene glycol) diacrylate (PEGDA) hydrogel to mimic the liver metabolism. The radical scavenging activity was evaluated by the change of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) absorbance in the second compartment. Reaction engineering and fluid mechanics principles were used to develop a simplified analytical model and a more complex finite element model, which were used to design the chip and determine the optimal flow conditions. For real-time measurements of the reaction on a chip, we developed a custom-made photospectrometer system with an LED light source. The developed microfluidic system showed a linear and dose-dependent antioxidant activity in response to increasing concentration of flavonoid. We also compared the antioxidant activity of flavonoid after various liver metabolic reactions. This microfluidic system can serve as a novel in vitro platform for predicting the antioxidant activity of various food components in a more physiologically realistic manner, as well as for studying the mechanism of action of such food components.

  13. Flexibility in metabolic rate and activity level determines individual variation in overwinter performance.

    PubMed

    Auer, Sonya K; Salin, Karine; Anderson, Graeme J; Metcalfe, Neil B

    2016-11-01

    Energy stores are essential for the overwinter survival of many temperate and polar animals, but individuals within a species often differ in how quickly they deplete their reserves. These disparities in overwinter performance may be explained by differences in their physiological and behavioral flexibility in response to food scarcity. However, little is known about whether individuals exhibit correlated or independent changes in these traits, and how these phenotypic changes collectively affect their winter energy use. We examined individual flexibility in both standard metabolic rate and activity level in response to food scarcity and their combined consequences for depletion of lipid stores among overwintering brown trout (Salmo trutta). Metabolism and activity tended to decrease, yet individuals exhibited striking differences in their physiological and behavioral flexibility. The rate of lipid depletion was negatively related to decreases in both metabolic and activity rates, with the smallest lipid loss over the simulated winter period occurring in individuals that had the greatest reductions in metabolism and/or activity. However, changes in metabolism and activity were negatively correlated; those individuals that decreased their SMR to a greater extent tended to increase their activity rates, and vice versa, suggesting among-individual variation in strategies for coping with food scarcity.

  14. Comparison of cortical activation in an upper limb added-purpose task versus a single-purpose task: a near-infrared spectroscopy study.

    PubMed

    Huang, Fubiao; Hirano, Daisuke; Shi, Yun; Taniguchi, Takamichi

    2015-12-01

    [Purpose] The purpose of this study was to compare prefrontal activations during an added-purpose task with those during a single-purpose task using functional near-infrared spectroscopy. [Subjects] Six healthy right-handed adults were included in this study. [Methods] The participants were instructed to complete both added-purpose and single-purpose activities separately with each hand. The near-infrared spectroscopy probes were placed on the scalp overlying the prefrontal cortex, according to the International 10-20 system (Fz). Changes in the oxygenated hemoglobin and deoxygenated hemoglobin concentrations in the prefrontal cortex were measured during performance of the activities. We then compared the number of activation channels with significant increase in oxygenated hemoglobin, during added-purpose activity to single-purpose activity using both hands separately. [Results] A greater number of widespread activations were observed in the prefrontal cortex during the added-purpose task than during the single-purpose task. These results were noted with both right and left hands. [Conclusion] According to our findings, added-purpose activity can bring about more activation in the prefrontal cortex, which may provide occupational therapists with effective guides in therapeutic practice.

  15. A Metabolic Biofuel Cell: Conversion of Human Leukocyte Metabolic Activity to Electrical Currents

    PubMed Central

    2011-01-01

    An investigation of the electrochemical activity of human white blood cells (WBC) for biofuel cell (BFC) applications is described. WBCs isolated from whole human blood were suspended in PBS and introduced into the anode compartment of a proton exchange membrane (PEM) fuel cell. The cathode compartment contained a 50 mM potassium ferricyanide solution. Average current densities between 0.9 and 1.6 μA cm-2 and open circuit potentials (Voc) between 83 and 102 mV were obtained, which were both higher than control values. Cyclic voltammetry was used to investigate the electrochemical activity of the activated WBCs in an attempt to elucidate the mechanism of electron transfer between the cells and electrode. Voltammograms were obtained for the WBCs, including peripheral blood mononuclear cells (PBMCs - a lymphocyte-monocyte mixture isolated on a Ficoll gradient), a B lymphoblastoid cell line (BLCL), and two leukemia cell lines, namely K562 and Jurkat. An oxidation peak at about 363 mV vs. SCE for the PMA (phorbol ester) activated primary cells, with a notable absence of a reduction peak was observed. Oxidation peaks were not observed for the BLCL, K562 or Jurkat cell lines. HPLC confirmed the release of serotonin (5-HT) from the PMA activated primary cells. It is believed that serotonin, among other biochemical species released by the activated cells, contributes to the observed BFC currents. PMID:21569243

  16. Addressing metabolic activation as an integral component of drug design.

    PubMed

    Doss, George A; Baillie, Thomas A

    2006-01-01

    Formation of reactive intermediates by metabolism of xenobiotics represents a potential liability in drug discovery and development. Although it is difficult, if not impossible, to predict toxicities of drug candidates accurately, it is prudent to try to minimize bioactivation liabilities as early as possible in the stage of drug discovery and lead optimization. Measurement of covalent binding to liver microsomal proteins in the presence and the absence of NADPH, as well as the use of trapping agents such as glutathione or cyanide ions to provide structural information on reactive intermediates, have been used routinely to screen drug candidates. These in vitro experiments are often supplemented with in vivo covalent binding data in rats. The resulting data are not only used to eliminate potentially risky compounds, but, more importantly, they provide invaluable information to direct the Medicinal Chemistry group efforts to design analogs with less propensity to undergo bioactivation. Select case histories are presented in which this approach was successfully applied at Merck.

  17. Mapping Metabolic Brain Activity in Three Models of Hepatic Encephalopathy

    PubMed Central

    Méndez, Marta; Fidalgo, Camino; Aller, María Ángeles; Arias, Jaime; Arias, Jorge L.

    2013-01-01

    Cirrhosis is a common disease in Western countries. Liver failure, hyperammonemia, and portal hypertension are the main factors that contribute to human cirrhosis that frequently leads to a neuropsychiatric disorder known as hepatic encephalopathy (HE). In this study, we examined the differential contribution of these leading factors to the oxidative metabolism of diverse brain limbic system regions frequently involved in memory process by histochemical labelling of cytochrome oxidase (COx). We have analyzed cortical structures such as the infralimbic and prelimbic cotices, subcortical structures such as hippocampus and ventral striatum, at thalamic level like the anterodorsal, anteroventral, and mediodorsal thalamus, and, finally, the hypothalamus, where the mammillary nuclei (medial and lateral) were measured. The severest alteration is found in the model that mimics intoxication by ammonia, followed by the thioacetamide-treated group and the portal hypertension group. No changes were found at the mammillary bodies for any of the experimental groups. PMID:23573412

  18. Activation of eicosanoid metabolism in human airway epithelial cells by ozonolysis products of membrane fatty acids.

    PubMed

    Leikauf, G D; Zhao, Q; Zhou, S; Santrock, J

    1995-09-01

    Inhaled ozone can react with a variety of cellular macromolecules within the lung. Recent analyses of the chemistry of ozone reactions with unsaturated fatty acids, which are present in all membranes and in mucus in the airways, indicate that ozonolysis yields one aldehyde and one hydroxyhydroperoxide molecule for each molecule of ozone. The hydroxyhydroperoxide molecule is unstable in aqueous environments, and subsequently yields a second aldehyde and hydrogen peroxide. The structure of common unsaturated fatty acids is such that attack by ozone at the carbon-carbon double bonds will yield 3-, 6-, and 9-carbon saturated and unsaturated aldehydes and hydroxyhydroperoxide. This study examines the effects of ozonolysis products on eicosanoid metabolism in human airway epithelial cells. Eicosanoid biosynthesis is important in a wide array of pathophysiological responses in the airway, and the release of eicosanoids by the epithelial barrier is likely to be significant in diseases induced by environmental factors. Previously, we demonstrated that ozone can increase eicosanoid synthesis from airway epithelial cells exposed in vitro. Human exposures to concentrations of ozone below the current National Ambient Air Quality Standard (0.12 ppm, not to be exceeded for more than one hour once per year) also resulted in increased eicosanoids in bronchoalveolar lavage fluid. To determine whether ozonolysis products could activate eicosanoid release, we exposed human airway epithelial cells to 3-, 6-, and 9-carbon aldehydes, hydroxyhydroperoxides, and hydrogen peroxide. We measured (1) eicosanoid metabolism using high-performance liquid chromatography and radioimmunoassays, and (2) the effects of the aldehydes, hydroxyhydroperoxides, and hydrogen peroxide on cell lysis. Eicosanoid release increased after exposure to aldehyde; release induced by 9-carbon (nonanal) aldehyde was greater than that induced by the 6-carbon (hexanal) or 3-carbon (propanal) aldehydes

  19. Integration of light and metabolic signals for stem cell activation at the shoot apical meristem

    PubMed Central

    Pfeiffer, Anne; Janocha, Denis; Dong, Yihan; Medzihradszky, Anna; Schöne, Stefanie; Daum, Gabor; Suzaki, Takuya; Forner, Joachim; Langenecker, Tobias; Rempel, Eugen; Schmid, Markus; Wirtz, Markus; Hell, Rüdiger; Lohmann, Jan U

    2016-01-01

    A major feature of embryogenesis is the specification of stem cell systems, but in contrast to the situation in most animals, plant stem cells remain quiescent until the postembryonic phase of development. Here, we dissect how light and metabolic signals are integrated to overcome stem cell dormancy at the shoot apical meristem. We show on the one hand that light is able to activate expression of the stem cell inducer WUSCHEL independently of photosynthesis and that this likely involves inter-regional cytokinin signaling. Metabolic signals, on the other hand, are transduced to the meristem through activation of the TARGET OF RAPAMYCIN (TOR) kinase. Surprisingly, TOR is also required for light signal dependent stem cell activation. Thus, the TOR kinase acts as a central integrator of light and metabolic signals and a key regulator of stem cell activation at the shoot apex. DOI: http://dx.doi.org/10.7554/eLife.17023.001 PMID:27400267

  20. FOXO1 couples metabolic activity and growth state in the vascular endothelium

    PubMed Central

    Wilhelm, Kerstin; Happel, Katharina; Eelen, Guy; Schoors, Sandra; Oellerich, Mark F.; Lim, Radiance; Zimmermann, Barbara; Aspalter, Irene M.; Franco, Claudio A.; Boettger, Thomas; Braun, Thomas; Fruttiger, Marcus; Rajewsky, Klaus; Keller, Charles; Brüning, Jens C.; Gerhardt, Holger; Carmeliet, Peter; Potente, Michael

    2015-01-01

    Endothelial cells (ECs) are plastic cells that can switch between growth states with different bioenergetic and biosynthetic requirements1. Although quiescent in most healthy tissues, ECs divide and migrate rapidly upon proangiogenic stimulation2,3. Adjusting endothelial metabolism to growth state is central to normal vessel growth and function1,4, yet poorly understood at the molecular level. Here we report that the forkhead box O (FOXO) transcription factor FOXO1 is an essential regulator of vascular growth that couples metabolic and proliferative activities in ECs. Endothelial-restricted deletion of FOXO1 in mice induces a profound increase in EC proliferation that interferes with coordinated sprouting, thereby causing hyperplasia and vessel enlargement. Conversely, forced expression of FOXO1 restricts vascular expansion and leads to vessel thinning and hypobranching. We find that FOXO1 acts as a gatekeeper of endothelial quiescence, which decelerates metabolic activity by reducing glycolysis and mitochondrial respiration. Mechanistically, FOXO1 suppresses signalling by c-MYC (termed MYC hereafter), a powerful driver of anabolic metabolism and growth5,6. MYC ablation impairs glycolysis, mitochondrial function and proliferation of ECs while its EC-specific overexpression fuels these processes. Moreover, restoration of MYC signalling in FOXO1-overexpressing endothelium normalises metabolic activity and branching behaviour. Our findings identify FOXO1 as a critical rheostat of vascular expansion and define the FOXO1 – MYC transcriptional network as a novel metabolic checkpoint during endothelial growth and proliferation. PMID:26735015

  1. Systems biology network-based discovery of a small molecule activator BL-AD008 targeting AMPK/ZIPK and inducing apoptosis in cervical cancer

    PubMed Central

    Tong, Xupeng; Zhang, Jin; Zhang, Yonghui; Ouyang, Liang; Liu, Bo; Huang, Jian

    2015-01-01

    The aim of this study was to discover a small molecule activator BL-AD008 targeting AMPK/ZIPK and inducing apoptosis in cervical cancer. In this study, we systematically constructed the global protein-protein interaction (PPI) network and predicted apoptosis-related protein connections by the Naïve Bayesian model. Then, we identified some classical apoptotic PPIs and other previously unrecognized PPIs between apoptotic kinases, such as AMPK and ZIPK. Subsequently, we screened a series of candidate compounds targeting AMPK/ZIPK, synthesized some compounds and eventually discovered a novel dual-target activator (BL-AD008). Moreover, we found BL-AD008 bear remarkable anti-proliferative activities toward cervical cancer cells and could induce apoptosis by death-receptor and mitochondrial pathways. Additionally, we found that BL-AD008-induced apoptosis was affected by the combination of AMPK and ZIPK. Then, we found that BL-AD008 bear its anti-tumor activities and induced apoptosis by targeting AMPK/ZIPK in vivo. In conclusion, these results demonstrate the ability of systems biology network to identify some key apoptotic kinase targets AMPK and ZIPK; thus providing a dual-target small molecule activator (BL-AD008) as a potential new apoptosis-modulating drug in future cervical cancer therapy. PMID:25797270

  2. [The effect of limiting neuronal energy metabolism on the level of impulse activity and membrane potentials].

    PubMed

    Voronova, N V; Chumachenko, A A

    1989-01-01

    The changes of the membrane potential and the frequency of impulse activity of the crayfish stretch receptor neuron have been studied under condition of energy supply deficiency. The energetic metabolism inhibitors have been found not to exert a significant effect on the membrane potential. The activity of the glycolysis process and the Krebs cycle have different effect on the sensitivity of the generating mechanism.

  3. Phytase activity as a novel metabolic feature in Bifidobacterium.

    PubMed

    Haros, Monica; Bielecka, Maria; Sanz, Yolanda

    2005-06-15

    Phytase activity has been detected for the first time in Bifidobacterium spp. These bacteria were able to dephosphorylate phytic acid (myo-inositol hexaphosphate, IP(6)) and generate several myo-inositol phosphate intermediates (IP(3)-IP(5)). B. globosum and B. pseudocatenulatum were optimally active at neutral-alkaline pH and B. adolescentis, B. angulatum and B. longum at acid pH. B. pseudocatenulatum showed the highest levels of phytase activity. This species produced maximum activity in the exponential phase of growth and when fructo-oligosaccharides were used as carbon source in the culture medium. The potential role of phytase activity from Bifidobacterium spp. in the reduction of the antinutritional properties of IP(6) is discussed.

  4. Spore Germination and Carbon Metabolism in Fusarium solani V. Changes in Anaerobic Metabolism and Related Enzyme Activities during Development 1

    PubMed Central

    Cochrane, Vincent W.; Cochrane, Jean C.

    1966-01-01

    Macroconidia of Fusarium solani f. phascoli have no detectable capacity to respire glucose anaerobically; germinated spores and mycelium, on the other hand, ferment glucose, although slowly. Extracts of ungerminated spores contain hexokinase, phosphohexoisomerase, phosphofructokinase, aldolase, triose phosphate dehydrogenase, triose phosphate isomerase, phosphoglyceric kinase, enolase, phosphoglyceric mutase, pyruvate kinase, and pyruvate decarboxylase. It follows, therefore, that the appearance of fermentative capacity during spore germination cannot be ascribed to the de novo synthesis of any of these enzymes. During germination and mycelial development the specific activity of all of the enzymes named except phosphohexoisomerase and aldolase increases 2- to 8-fold. Specific activity of all of the enzymes is substantially higher than the fermentative capacity of intact cells, i.e., none is limiting to anaerobic respiration. The enzymatic assay data are consistent with a conclusion reached earlier on the basis of studies of aerobic glucose metabolism, that the process of germination involves an acceleration of pre-existing metabolic systems rather than an appearance of new pathways. PMID:16656324

  5. Intranasal insulin restores insulin signaling, increases synaptic proteins, and reduces Aβ level and microglia activation in the brains of 3xTg-AD mice.

    PubMed

    Chen, Yanxing; Zhao, Yang; Dai, Chun-Ling; Liang, Zhihou; Run, Xiaoqin; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

    2014-11-01

    Decreased brain insulin signaling has been found recently in Alzheimer's disease (AD). Intranasal administration of insulin, which delivers the drug directly into the brain, improves memory and cognition in both animal studies and small clinical trials. However, the underlying mechanisms are unknown. Here, we treated 9-month-old 3xTg-AD mice, a commonly used mouse model of AD, with daily intranasal administration of insulin for seven days and then studied brain abnormalities of the mice biochemically and immunohistochemically. We found that intranasal insulin restored insulin signaling, increased the levels of synaptic proteins, and reduced Aβ40 level and microglia activation in the brains of 3xTg-AD mice. However, this treatment did not affect the levels of glucose transporters and O-GlcNAcylation or tau phosphorylation. Our findings provide a mechanistic insight into the beneficial effects of intranasal insulin treatment and support continuous clinical trials of intranasal insulin for the treatment of AD.

  6. Added value of next generation gene panel analysis for patients with elevated methylmalonic acid and no clinical diagnosis following functional studies of vitamin B12 metabolism.

    PubMed

    Pupavac, Mihaela; Tian, Xia; Chu, Jordan; Wang, Guoli; Feng, Yanming; Chen, Stella; Fenter, Remington; Zhang, Victor W; Wang, Jing; Watkins, David; Wong, Lee-Jun; Rosenblatt, David S

    2016-03-01

    Next generation sequencing (NGS) based gene panel testing is increasingly available as a molecular diagnostic approach for inborn errors of metabolism. Over the past 40 years patients have been referred to the Vitamin B12 Clinical Research Laboratory at McGill University for diagnosis of inborn errors of cobalamin metabolism by functional studies in cultured fibroblasts. DNA samples from patients in which no diagnosis was made by these studies were tested by a NGS gene panel to determine whether any molecular diagnoses could be made. 131 DNA samples from patients with elevated methylmalonic acid and no diagnosis following functional studies of cobalamin metabolism were analyzed using the 24 gene extended cobalamin metabolism NGS based panel developed by Baylor Miraca Genetics Laboratories. Gene panel testing identified two or more variants in a single gene in 16/131 patients. Eight patients had pathogenic findings, one had a finding of uncertain significance, and seven had benign findings. Of the patients with pathogenic findings, five had mutations in ACSF3, two in SUCLG1 and one in TCN2. Thus, the NGS gene panel allowed for the presumptive diagnosis of 8 additional patients for which a diagnosis was not made by the functional assays.

  7. Peroxisome Proliferator-Activated Receptor γ 2 Modulates Late-Pregnancy Homeostatic Metabolic Adaptations

    PubMed Central

    Vivas, Yurena; Díez-Hochleitner, Monica; Izquierdo-Lahuerta, Adriana; Corrales, Patricia; Horrillo, Daniel; Velasco, Ismael; Martínez-García, Cristina; Campbell, Mark; Sevillano, Julio; Ricote, Mercedes; Ros, Manuel; Ramos, Maria Pilar; Medina-Gomez, Gema

    2016-01-01

    Pregnancy requires adaptation of maternal energy metabolism, including expansion and functional modifications of adipose tissue. Insulin resistance (IR), predominantly during late gestation, is a physiological metabolic adaptation that serves to support the metabolic demands of fetal growth. The molecular mechanisms underlying these adaptations are not fully understood and may contribute to gestational diabetes mellitus. Peroxisome proliferator-activated receptor γ (PPARγ) controls adipogenesis, glucose and lipid metabolism and insulin sensitivity. The PPARγ2 isoform is mainly expressed in adipocytes and is thus likely to contribute to adipose tissue adaptation during late pregnancy. In the present study, we investigated the contribution of PPARγ2 to the metabolic adaptations occurring during the late phase of pregnancy in the context of IR. Using a model of late pregnancy in PPARγ2 knockout (KO) mice, we found that deletion of PPARγ2 exacerbated IR in association with lower serum adiponectin levels, increased body weight and enhanced lipid accumulation in the liver. Lack of PPARγ2 provoked changes in the distribution of fat mass and preferentially prevented expansion of the perigonadal depot while at the same time exacerbating inflammation. Pregnant PPARγ2KO mice presented adipose tissue depot-dependent decreased expression of genes involved in lipid metabolism. Collectively, these data indicate that PPARγ2 is essential in promoting healthy adipose tissue expansion and immune and metabolic functionality during pregnancy, contributing to the physiological adaptations that lead gestation to term. PMID:27782293

  8. Enrichment of specific electro-active microorganisms and enhancement of methane production by adding granular activated carbon in anaerobic reactors.

    PubMed

    Lee, Jung-Yeol; Lee, Sang-Hoon; Park, Hee-Deung

    2016-04-01

    Direct interspecies electron transfer (DIET) via conductive materials can provide significant benefits to anaerobic methane formation in terms of production amount and rate. Although granular activated carbon (GAC) demonstrated its applicability in facilitating DIET in methanogenesis, DIET in continuous flow anaerobic reactors has not been verified. Here, evidences of DIET via GAC were explored. The reactor supplemented with GAC showed 1.8-fold higher methane production rate than that without GAC (35.7 versus 20.1±7.1mL-CH4/d). Around 34% of methane formation was attributed to the biomass attached to GAC. Pyrosequencing of 16S rRNA gene demonstrated the enrichment of exoelectrogens (e.g. Geobacter) and hydrogenotrophic methanogens (e.g. Methanospirillum and Methanolinea) from the biomass attached to GAC. Furthermore, anodic and cathodic currents generation was observed in an electrochemical cell containing GAC biomass. Taken together, GAC supplementation created an environment for enriching the microorganisms involved in DIET, which increased the methane production rate.

  9. Transformation of steroids by Bacillus strains isolated from the foregut of water beetles (Coleoptera:Dytiscidae): I. Metabolism of androst-4-en-3,17-dione (AD).

    PubMed

    Schaaf, O; Dettner, K

    1998-12-01

    Two Bacillus strains were isolated from the foregut of the water beetle Agabus affinis (Payk.) and tested for their steroid transforming ability. After incubation with androst-4-en-3,17-dione (AD), 13 different transformation products were detected. AD was hydroxylated at C6, C7, C11 and C14, resulting in formation of 6beta-, 7alpha-, 11alpha- and 14alpha-hydroxy-AD. One strain also produced small amounts of 6beta,14alpha-dihydroxy-AD. Partly, the 6beta-hydroxy group was further oxidized to the corresponding 6-oxo steroids. In addition, a specific reduction of the delta4-double bond was observed, leading to the formation of 5alpha-androstane derivatives. In minor yields the carbonyl functions at C3 and C17 were reduced leading to the formation of 3zeta-OH or 17beta-OH steroids. EI mass spectra of the trimethylsilyl and O-methyloxime trimethylsilyl ether derivatives of some transformation products are presented for the first time.

  10. Glutamine activates STAT3 to control cancer cell proliferation independently of glutamine metabolism.

    PubMed

    Cacace, A; Sboarina, M; Vazeille, T; Sonveaux, P

    2017-04-01

    Cancer cells can use a variety of metabolic substrates to fulfill the bioenergetic and biosynthetic needs of their oncogenic program. Besides bioenergetics, cancer cell metabolism also directly influences genetic, epigenetic and signaling events associated with tumor progression. Many cancer cells are addicted to glutamine, and this addiction is observed in oxidative as well as in glycolytic cells. Although both oxidative and bioreductive glutamine metabolism can contribute to cancer progression and glutamine can further serve to generate peptides (including glutathione) and proteins, we report that glutamine promotes the proliferation of cancer cells independently of its use as a metabolic fuel or as a precursor of glutathione. Extracellular glutamine activates transcription factor signal transducer and activator of transcription 3 (STAT3), which is necessary and sufficient to mediate the proliferative effects of glutamine on glycolytic and oxidative cancer cells. Glutamine also activates transcription factors hypoxia-inducible factor-1, mammalian target of rapamycin and c-Myc, but these factors do not mediate the effects of glutamine on cancer cell proliferation. Our findings shed a new light on the anticancer effects of l-asparaginase that possesses glutaminase activity and converts glutamine into glutamate extracellularly. Conversely, cancer resistance to treatments that block glutamine metabolism could arise from glutamine-independent STAT3 reactivation.

  11. Disturbances to neurotransmitter levels and their metabolic enzyme activity in a freshwater planarian exposed to cadmium.

    PubMed

    Wu, Jui-Pin; Li, Mei-Hui; Chen, Jhih-Sheng; Chung, Szu-Yao; Lee, Hui-Ling

    2015-03-01

    Using specific neurobehaviors as endpoints, previous studies suggested that planarian neurotransmission systems could be targets of Cd neurotoxicity. However, direct evidence for disturbed neurotransmission systems by Cd in treated planarians is still lacking. In planarians, dopamine (DA) and serotonin (5-HT) play critical roles in neuromuscular function, but little is known about their metabolic degradation. Therefore, in this study, we attempted to determine the appearances of DA, 5-HT, and their metabolic products in the freshwater planarian Dugesia japonica, characterize the activity of enzymes involved in their metabolism, and investigate the effects of Cd on planarian 5-HTergic and DAergic neurotransmission systems. Only DA, 5-HT, and 5-hydroxyindole-3-acetic acid (5-HIAA) were found in planarian tissues. Further enzymatic study revealed the activity of planarian monoamine oxidase (MAO) but not catechol-O-methyl transferase (COMT). These findings suggest that planarian MAO catalyzes the metabolism of 5-HT into 5-HIAA. However, DA metabolites from the MAO-involved metabolic pathway were not found, which might be due to a lack of COMT activity. Finally, in Cd-treated planarians, tissue levels of 5-HT and DA were decreased and MAO activity altered, suggesting that planarian neurotransmission systems are disturbed following Cd treatment.

  12. The connexion between active cation transport and metabolism in erythrocytes

    PubMed Central

    Whittam, R.; Ager, Margaret E.

    1965-01-01

    1. A study has been made of the dependence on the concentrations of internal Na+ and external K+ of lactate and phosphate production in human erythrocytes. 2. Lactate production was stimulated by Na+ and K+ but only when they were internal and external respectively. The stimulation was counteracted by ouabain. The production of phosphate was affected in the same way. 3. There is a quantitative correlation between these effects and those previously found for cation movements and the membrane adenosine triphosphatase. 4. It is concluded that the rate of energy production in glycolysis is partly controlled by the magnitude of active transport; the extent of this regulation is shown to vary from 25 to 75% of a basal rate that is independent of active transport. 5. The activity of the membrane adenosine triphosphatase was also compared with rates of Na+ and K+ transport. The latter were varied by altering the concentrations of internal Na+ and external K+, and by inhibiting with ouabain. 6. A threefold variation of active transport rate was accompanied by a parallel change in the membrane adenosine-triphosphatase activity. The results show a constant stoicheiometry for the number of ions moved/mol. of ATP hydrolysed, independent of the electrochemical gradient against which the ions were moved. 7. Calculations show that the amount of ATP hydrolysed would provide enough energy for the osmotic work. The results are discussed in relation to possible mechanisms for active transport. PMID:16749106

  13. Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cells

    PubMed Central

    Choi, S.; Sainz, B.; Corcoran, P.; Uprichard, S.; Jeong, H.

    2010-01-01

    1. The objective of this study was to characterize Huh7 cells' baseline capacity to metabolize drugs and to investigate whether the drug metabolism was enhanced upon treatment with dimethyl sulfoxide (DMSO). 2. The messenger RNA (mRNA) levels of major Phase I and Phase II enzymes were determined by quantitative real-time-polymerase chain reaction (RT-PCR), and activities of major drug-metabolizing enzymes were examined using probe drugs by analysing relevant metabolite production rates. 3. The expression levels of drug-metabolizing enzymes in control Huh7 cells were generally very low, but DMSO treatment dramatically increased the mRNA levels of most drug-metabolizing enzymes as well as other liver-specific proteins. Importantly, functionality assays confirmed concomitant increases in drug-metabolizing enzyme activity. Additionally, treatment of the Huh7 cells with 3-methylcholanthrene induced cytochrome P450 (CYP) 1A1 expression. 4. The results indicate that DMSO treatment of Huh7 cells profoundly enhances their differentiation state, thus improving the usefulness of this common cell line as an in vitro hepatocyte model. PMID:19280519

  14. c-Myc activates multiple metabolic networks to generate substrates for cell-cycle entry.

    PubMed

    Morrish, F; Isern, N; Sadilek, M; Jeffrey, M; Hockenbery, D M

    2009-07-09

    Cell proliferation requires the coordinated activity of cytosolic and mitochondrial metabolic pathways to provide ATP and building blocks for DNA, RNA and protein synthesis. Many metabolic pathway genes are targets of the c-myc oncogene and cell-cycle regulator. However, the contribution of c-Myc to the activation of cytosolic and mitochondrial metabolic networks during cell-cycle entry is unknown. Here, we report the metabolic fates of [U-(13)C] glucose in serum-stimulated myc(-/-) and myc(+/+) fibroblasts by (13)C isotopomer NMR analysis. We demonstrate that endogenous c-myc increased (13)C labeling of ribose sugars, purines and amino acids, indicating partitioning of glucose carbons into C1/folate and pentose phosphate pathways, and increased tricarboxylic acid cycle turnover at the expense of anaplerotic flux. Myc expression also increased global O-linked N-acetylglucosamine protein modification, and inhibition of hexosamine biosynthesis selectively reduced growth of Myc-expressing cells, suggesting its importance in Myc-induced proliferation. These data reveal a central organizing function for the Myc oncogene in the metabolism of cycling cells. The pervasive deregulation of this oncogene in human cancers may be explained by its function in directing metabolic networks required for cell proliferation.

  15. Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cells.

    PubMed

    Choi, S; Sainz, B; Corcoran, P; Uprichard, S; Jeong, H

    2009-03-01

    The objective of this study was to characterize Huh7 cells' baseline capacity to metabolize drugs and to investigate whether the drug metabolism was enhanced upon treatment with dimethyl sulfoxide (DMSO). The messenger RNA (mRNA) levels of major Phase I and Phase II enzymes were determined by quantitative real-time-polymerase chain reaction (RT-PCR), and activities of major drug-metabolizing enzymes were examined using probe drugs by analysing relevant metabolite production rates. The expression levels of drug-metabolizing enzymes in control Huh7 cells were generally very low, but DMSO treatment dramatically increased the mRNA levels of most drug-metabolizing enzymes as well as other liver-specific proteins. Importantly, functionality assays confirmed concomitant increases in drug-metabolizing enzyme activity. Additionally, treatment of the Huh7 cells with 3-methylcholanthrene induced cytochrome P450 (CYP) 1A1 expression. The results indicate that DMSO treatment of Huh7 cells profoundly enhances their differentiation state, thus improving the usefulness of this common cell line as an in vitro hepatocyte model.

  16. Adding Value.

    ERIC Educational Resources Information Center

    Orsini, Larry L.; Hudack, Lawrence R.; Zekan, Donald L.

    1999-01-01

    The value-added statement (VAS), relatively unknown in the United States, is used in financial reports by many European companies. Saint Bonaventure University (New York) has adapted a VAS to make it appropriate for not-for-profit universities by identifying stakeholder groups (students, faculty, administrators/support personnel, creditors, the…

  17. Muscle Transcriptional Profile Based on Muscle Fiber, Mitochondrial Respiratory Activity, and Metabolic Enzymes

    PubMed Central

    Liu, Xuan; Du, Yang; Trakooljul, Nares; Brand, Bodo; Muráni, Eduard; Krischek, Carsten; Wicke, Michael; Schwerin, Manfred; Wimmers, Klaus; Ponsuksili, Siriluck

    2015-01-01

    Skeletal muscle is a highly metabolically active tissue that both stores and consumes energy. Important biological pathways that affect energy metabolism and metabolic fiber type in muscle cells may be identified through transcriptomic profiling of the muscle, especially ante mortem. Here, gene expression was investigated in malignant hyperthermia syndrome (MHS)-negative Duroc and Pietrian (PiNN) pigs significantly differing for the muscle fiber types slow-twitch-oxidative fiber (STO) and fast-twitch-oxidative fiber (FTO) as well as mitochondrial activity (succinate-dependent state 3 respiration rate). Longissimus muscle samples were obtained 24 h before slaughter and profiled using cDNA microarrays. Differential gene expression between Duroc and PiNN muscle samples were associated with protein ubiquitination, stem cell pluripotency, amyloid processing, and 3-phosphoinositide biosynthesis and degradation pathways. In addition, weighted gene co-expression network analysis within both breeds identified several co-expression modules that were associated with the proportion of different fiber types, mitochondrial respiratory activity, and ATP metabolism. In particular, Duroc results revealed strong correlations between mitochondrion-associated co-expression modules and STO (r = 0.78), fast-twitch glycolytic fiber (r = -0.98), complex I (r=0.72) and COX activity (r = 0.86). Other pathways in the protein-kinase-activity enriched module were positively correlated with STO (r=0.93), while negatively correlated with FTO (r = -0.72). In contrast to PiNN, co-expression modules enriched in macromolecule catabolic process, actin cytoskeleton, and transcription activator activity were associated with fiber types, mitochondrial respiratory activity, and metabolic enzyme activities. Our results highlight the importance of mitochondria for the oxidative capacity of porcine muscle and for breed-dependent molecular pathways in muscle cell fibers. PMID:26681915

  18. Carbohydrate starvation causes a metabolically active but nonculturable state in Lactococcus lactis.

    PubMed

    Ganesan, Balasubramanian; Stuart, Mark R; Weimer, Bart C

    2007-04-01

    This study characterized the ability of lactococci to become nonculturable under carbohydrate starvation while maintaining metabolic activity. We determined the changes in physiological parameters and extracellular substrate levels of multiple lactococcal strains under a number of environmental conditions along with whole-genome expression profiles. Three distinct phases were observed, logarithmic growth, sugar exhaustion, and nonculturability. Shortly after carbohydrate starvation, each lactococcal strain lost the ability to form colonies on solid media but maintained an intact cell membrane and metabolic activity for over 3.5 years. ML3, a strain that metabolized lactose rapidly, reached nonculturability within 1 week. Strains that metabolized lactose slowly (SK11) or not at all (IL1403) required 1 to 3 months to become nonculturable. In all cases, the cells contained at least 100 pM of intracellular ATP after 6 months of starvation and remained at that level for the remainder of the study. Aminopeptidase and lipase/esterase activities decreased below detection limits during the nonculturable phase. During sugar exhaustion and entry into nonculturability, serine and methionine were produced, while glutamine and arginine were depleted from the medium. The cells retained the ability to transport amino acids via proton motive force and peptides via ATP-driven translocation. The addition of branched-chain amino acids to the culture medium resulted in increased intracellular ATP levels and new metabolic products, indicating that branched-chain amino acid catabolism resulted in energy and metabolic products to support survival during starvation. Gene expression analysis showed that the genes responsible for sugar metabolism were repressed as the cells entered nonculturability. The genes responsible for cell division were repressed, while autolysis and cell wall metabolism genes were induced neither at starvation nor during nonculturability. Taken together, these

  19. Carbohydrate Starvation Causes a Metabolically Active but Nonculturable State in Lactococcus lactis▿ † ‡

    PubMed Central

    Ganesan, Balasubramanian; Stuart, Mark R.; Weimer, Bart C.

    2007-01-01

    This study characterized the ability of lactococci to become nonculturable under carbohydrate starvation while maintaining metabolic activity. We determined the changes in physiological parameters and extracellular substrate levels of multiple lactococcal strains under a number of environmental conditions along with whole-genome expression profiles. Three distinct phases were observed, logarithmic growth, sugar exhaustion, and nonculturability. Shortly after carbohydrate starvation, each lactococcal strain lost the ability to form colonies on solid media but maintained an intact cell membrane and metabolic activity for over 3.5 years. ML3, a strain that metabolized lactose rapidly, reached nonculturability within 1 week. Strains that metabolized lactose slowly (SK11) or not at all (IL1403) required 1 to 3 months to become nonculturable. In all cases, the cells contained at least 100 pM of intracellular ATP after 6 months of starvation and remained at that level for the remainder of the study. Aminopeptidase and lipase/esterase activities decreased below detection limits during the nonculturable phase. During sugar exhaustion and entry into nonculturability, serine and methionine were produced, while glutamine and arginine were depleted from the medium. The cells retained the ability to transport amino acids via proton motive force and peptides via ATP-driven translocation. The addition of branched-chain amino acids to the culture medium resulted in increased intracellular ATP levels and new metabolic products, indicating that branched-chain amino acid catabolism resulted in energy and metabolic products to support survival during starvation. Gene expression analysis showed that the genes responsible for sugar metabolism were repressed as the cells entered nonculturability. The genes responsible for cell division were repressed, while autolysis and cell wall metabolism genes were induced neither at starvation nor during nonculturability. Taken together, these

  20. Understanding Fatty Acid Metabolism through an Active Learning Approach

    ERIC Educational Resources Information Center

    Fardilha, M.; Schrader, M.; da Cruz e Silva, O. A. B.; da Cruz e Silva, E. F.

    2010-01-01

    A multi-method active learning approach (MALA) was implemented in the Medical Biochemistry teaching unit of the Biomedical Sciences degree at the University of Aveiro, using problem-based learning as the main learning approach. In this type of learning strategy, students are involved beyond the mere exercise of being taught by listening. Less…

  1. Metabolic activity of sperm cells: correlation with sperm cell concentration, viability and motility in the rabbit.

    PubMed

    Sabés-Alsina, Maria; Planell, Núria; Gil, Sílvia; Tallo-Parra, Oriol; Maya-Soriano, Maria José; Taberner, Ester; Piles, Miriam; Sabés, Manel; Lopez-Bejar, Manel

    2016-10-01

    The resazurin reduction test (RRT) is a useful technique to assess the metabolic rate of sperm cells. RRT depends on the ability of metabolically active cells to reduce the non-fluorescent dye resazurin to the fluorescent resorufin. The aim of this study was to develop a vital fluorometric method to evaluate metabolic activity of rabbit sperm cells. Twenty-five rabbit males were included in the study. Viability and morphology, motility and metabolic activity were evaluated using an eosin-nigrosin staining, a computer-assisted semen analysis (CASA) and the RRT, respectively. Spearman rank correlation analysis was used to determine the correlation between RRT and semen parameters. After evaluation, a concentration of 10 × 106 sperm cells/ml was selected for further experiments with RRT. No significant correlation was found between the RRT results and the motility parameters. However, after RRT a significant positive correlation between relative fluorescence units and the percentage of alive spermatozoa (r = 0.62; P = 0.001) and a negative one with the percentage of sperm cells with acrosomic abnormalities (r = -0.45; P < 0.05) were detected. The vital assessment of metabolic rate of sperm cells by RRT could provide more information about semen quality than other routine semen analysis, correlating with sperm viability and acrosome status information.

  2. Diminished leptin signaling can alter circadian rhythm of metabolic activity and feeding.

    PubMed

    Hsuchou, Hung; Wang, Yuping; Cornelissen-Guillaume, Germaine G; Kastin, Abba J; Jang, Eunjin; Halberg, Franz; Pan, Weihong

    2013-10-01

    Leptin, a hormone mainly produced by fat cells, shows cell-specific effects to regulate feeding and metabolic activities. We propose that an important feature of metabolic dysregulation resulting in obesity is the loss of the circadian rhythm of biopotentials. This was tested in the pan-leptin receptor knockout (POKO) mice newly generated in our laboratory. In the POKO mice, leptin no longer induced pSTAT-3 signaling after intracerebroventricular injection. Three basic phenotypes were observed: the heterozygotes had similar weight and adiposity as the wild-type (WT) mice (>60% of the mice); the homozygotes were either fatter (∼30%), or rarely leaner (<5%) than the WT mice. By early adulthood, the POKO mice had higher average body weight and adiposity than their respective same-sex WT littermate controls, and this was consistent among different batches. The homozygote fat POKO showed significant reduction of midline estimating statistic of rhythm of circadian parameters, and shifts of ultradian rhythms. The blunted circadian rhythm of these extremely obese POKO mice was also seen in their physical inactivity, longer feeding bouts, and higher food intake. The extent of obesity correlated with the blunted circadian amplitude, accumulative metabolic and locomotor activities, and the severity of hyperphagia. This contrasts with the heterozygote POKO mice which showed little obesity and metabolic disturbance, and only subtle changes of the circadian rhythm of metabolic activity without alterations in feeding behavior. The results provide a novel aspect of leptin resistance, almost manifesting as an "all or none" phenomenon.

  3. Effects of cysteamine on growth performance, digestive enzyme activities, and metabolic hormones in broilers.

    PubMed

    Yang, C M; Chen, A G; Hong, Q H; Liu, J X; Liu, J S

    2006-11-01

    A total of 600 avian male broilers at the age of 1 d were used to investigate the effects of cysteamine (CSH) on growth performance, digestive enzyme activities, and concentrations of serum hormones. The broilers received the same basal diets, with CSH added at 0 (control), 60, 90, 120, or 150 mg/kg. The feeding program consisted of a starter diet until 21 d and a grower diet until 42 d. The broilers with addition of CSH at 60 or 90 mg/kg had significantly higher growth rates during d 1 to 21 or d 21 to 42 compared with the control, respectively. However, adding 150 mg of CSH/kg significantly suppressed the growth of broilers. Adding 60 mg of CSH/kg significantly increased the activities of protease, amylase, and lipase in the pancreas and small intestinal contents during d 1 to 21, and the activities of protease and amylase in the small intestinal contents during d 21 to 42. Adding 90 mg of CSH/kg significantly increased the activities of lipase during d 1 to 21 and protease, amylase, and lipase during d 21 to 42 in small intestines. The activities of digestive enzymes during the whole period were suppressed by adding 150 mg of CSH/kg. The concentration of serum thyroxine was higher in the CSH-added birds during the whole period, whereas serum triiodothyronine was higher only during d 1 to 21 compared with the control. These findings indicate that low doses of dietary CSH may improve the growth performance and the activities of the digestive enzyme, but high doses of CSH appear to be detrimental to growth and digestion.

  4. DMH1 increases glucose metabolism through activating Akt in L6 rat skeletal muscle cells.

    PubMed

    Xie, Xin; Xu, Xiao-Ming; Li, Na; Zhang, Yong-Hui; Zhao, Yu; Ma, Chun-Yan; Dong, De-Li

    2014-01-01

    DMH1(4-[6-(4-Isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl] quinoline) is a compound C analogue with the structural modifications at the 3- and 6-positions in pyrazolo[1,5-a]pyrimidine backbone. Compound C was reported to inhibit both AMPK and Akt. Our preliminary work found that DMH1 activated Akt. Since Akt was involved in glucose metabolism, we aimed to identify the effects of DMH1 on glucose metabolism in L6 rat muscle cells and the potential mechanism. Results showed that DMH1 increased lactic acid release and glucose consumption in L6 rat muscle cells in a dose-dependent manner. DMH1 activated Akt in L6 cells. Akt inhibitor inhibited DMH1-induced Akt activation and DMH1-induced increases of glucose uptake and consumption. DMH1 had no cytotoxicity in L6 cells, but inhibited mitochondrial function and reduced ATP production. DMH1 showed no effect on AMPK, but in the presence of Akt inhibitor, DMH1 significantly activated AMPK. Compound C inhibited DMH1-induced Akt activation in L6 cells. Compound C inhibited DMH1-induced increase of glucose uptake, consumption and lactic acid release in L6 cells. DMH1 inhibited PP2A activity, and PP2A activator forskolin reversed DMH1-induced Akt activation. We concluded that DMH1 increased glucose metabolism through activating Akt and DMH1 activated Akt through inhibiting PP2A activity in L6 rat muscle cells. In view of the analogue structure of DMH1 and compound C and the contrasting effects of DMH1 and compound C on Akt, the present study provides a novel leading chemical structure targeting Akt with potential use for regulating glucose metabolism.

  5. Timing and Variability of Galactose Metabolic Gene Activation Depend on the Rate of Environmental Change.

    PubMed

    Nguyen-Huu, Truong D; Gupta, Chinmaya; Ma, Bo; Ott, William; Josić, Krešimir; Bennett, Matthew R

    2015-07-01

    Modulation of gene network activity allows cells to respond to changes in environmental conditions. For example, the galactose utilization network in Saccharomyces cerevisiae is activated by the presence of galactose but repressed by glucose. If both sugars are present, the yeast will first metabolize glucose, depleting it from the extracellular environment. Upon depletion of glucose, the genes encoding galactose metabolic proteins will activate. Here, we show that the rate at which glucose levels are depleted determines the timing and variability of galactose gene activation. Paradoxically, we find that Gal1p, an enzyme needed for galactose metabolism, accumulates more quickly if glucose is depleted slowly rather than taken away quickly. Furthermore, the variability of induction times in individual cells depends non-monotonically on the rate of glucose depletion and exhibits a minimum at intermediate depletion rates. Our mathematical modeling suggests that the dynamics of the metabolic transition from glucose to galactose are responsible for the variability in galactose gene activation. These findings demonstrate that environmental dynamics can determine the phenotypic outcome at both the single-cell and population levels.

  6. Metabolism and growth inhibitory activity of cranberry derived flavonoids in bladder cancer cells.

    PubMed

    Prasain, Jeevan K; Rajbhandari, Rajani; Keeton, Adam B; Piazza, Gary A; Barnes, Stephen

    2016-09-14

    In the present study, anti-proliferative activities of cranberry derived flavonoids and some of their in vivo metabolites were evaluated using a panel of human bladder tumor cell lines (RT4, SCABER, and SW-780) and non-tumorigenic immortalized human uroepithelial cells (SV-HUC). Among the compounds tested, quercetin 3-O-glucoside, isorhamnetin (3'-O-methylquercetin), myricetin and quercetin showed strong concentration-dependent cell growth inhibitory activities in bladder cancer cells with IC50 values in a range of 8-92 μM. Furthermore, isorhamnetin and myricetin had very low inhibitory activity against SV-HUC even at very high concentrations (>200 μM) compared to bladder cancer cells, indicating that their cytotoxicity is selective for cancer cells. To determine whether the differential cell growth inhibitory effects of isomeric flavonoids quercetin 3-O-glucoside (active) and hyperoside (quercetin 3-O-galactoside) (inactive) are related to their metabolism by the cancer cells, SW-780 cells were incubated with these compounds and their metabolism was examined by LC-MS/MS. Compared to quercetin 3-O-glucoside, hyperoside undergoes relatively less metabolic biotransformation (methylation, glucuronidation and quinone formation). These data suggest that isorhamnetin and quercetin 3-O-glucoside may be the active forms of quercetin in prevention of bladder cancer in vivo and emphasize the importance of metabolism for the prevention of bladder cancer by diets rich in cranberries.

  7. Short term exposure to elevated levels of leptin reduces proximal tubule cell metabolic activity.

    PubMed

    Briffa, Jessica F; Grinfeld, Esther; McAinch, Andrew J; Poronnik, Philip; Hryciw, Deanne H

    2014-01-25

    Leptin plays a pathophysiological role in the kidney, however, its acute effects on the proximal tubule cells (PTCs) are unknown. In opossum kidney (OK) cells in vitro, Western blot analysis identified that exposure to leptin increases the phosphorylation of the mitogen-activated protein kinase (MAPK) p44/42 and the mammalian target of rapamycin (mTOR). Importantly leptin (0.05, 0.10, 0.25 and 0.50 μg/ml) significantly reduced the metabolic activity of PTCs, and significantly decreased protein content per cell. Investigation of the role of p44/42 and mTOR on metabolic activity and protein content per cell, demonstrated that in the presence of MAPK inhibitor U0126 and mTOR inhibitor Ku-63794, that the mTOR pathway is responsible for the reduction in PTC metabolic activity in response to leptin. However, p44/42 and mTOR play no role the reduced protein content per cell in OKs exposed to leptin. Therefore, leptin modulates metabolic activity in PTCs via an mTOR regulated pathway.

  8. [Biological activities of exogenous polysaccharides via controlling endogenous proteoglycan metabolism in vascular endothelial cells].

    PubMed

    Sato, Tomoko; Yamamoto, Chika; Fujiwara, Yasuyuki; Kaji, Toshiyuki

    2008-05-01

    Proteoglycan contains glycosmainoglycans, which are endogenous sulfated polysaccharides, in the molecule. The metabolism of proteoglycans regulates cell behavior and cellular events. It is possible that exogenous polysaccharide-related molecules exhibit their biological activities by two mechanisms. One is the interaction with cells and the other is the interaction with growth factors/cytokines that regulate proteoglycans. In this review, we describe sodium spirulan, a sulfated polysaccharide obtained from a hot-water extract of the blue-green alga Spirulina platensis, as an exogenous polysaccharide that stimulates the release of proteoglycans from vascular endothelial cells. Factors that regulate endothelial proteoglycan metabolism are also being described as possible target molecules of exogenous polysaccharides. Further research is required to obtain exogenous polysaccharide-related molecules that exhibit useful biological activities through controlling endothelial proteoglycan metabolism for protection against vascular lesions such as atheroslcerosis.

  9. Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans.

    PubMed

    Pontzer, Herman; Durazo-Arvizu, Ramon; Dugas, Lara R; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Cooper, Richard S; Schoeller, Dale A; Luke, Amy

    2016-02-08

    Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology.

  10. Metabolic and Co-Metabolic Transformation of Diclofenac by Enterobacter hormaechei D15 Isolated from Activated Sludge.

    PubMed

    Aissaoui, Salima; Ouled-Haddar, Houria; Sifour, Mohamed; Harrouche, Kamel; Sghaier, Haitham

    2017-03-01

    The presence of non-steroidal anti-inflammatory drugs, such as diclofenac (DCF), in the environment, is an emerging problem due to their harmful effects on non-target organisms, even at low concentrations. We studied the biodegradation of DCF by the strain D15 of Enterobacter hormaechei. The strain was isolated from an activated sludge, and identified as E. hormaechei based on its physiological characteristics and its 16 S RNA sequence. Using HPTLC and GC-MS methods, we demonstrated that this strain metabolized DCF at an elimination rate of 52.8%. In the presence of an external carbon source (glucose), the elimination rate increased to approximately 82%. GC-MS analysis detected and identified one metabolite as 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one; it was produced as a consequence of dehydration and lactam formation reactions.

  11. Variation in energy expenditure among black-legged kittiwakes: Effects of activity-specific metabolic rates and activity budgets

    USGS Publications Warehouse

    Jodice, P.G.R.; Roby, D.D.; Suryan, R.M.; Irons, D.B.; Kaufman, A.M.; Turco, K.R.; Visser, G. Henk

    2003-01-01

    We sought to determine the effect of variation in time-activity budgets (TABs) and foraging behavior on energy expenditure rates of parent black-legged kittiwakes (Rissa tridactyla). We quantified TABs using direct observations of radio-tagged adults and simultaneously measured field metabolic rates (FMR) of these same individuals (n = 20) using the doubly labeled water technique. Estimated metabolic rates of kittiwakes attending their brood at the nest or loafing near the colony were similar (ca. 1.3 x basal metabolic rate [BMR]), although loafing during foraging trips was more costly (2.9 x BMR). Metabolic rates during commuting flight (7.3 x BMR) and prey-searching flight (6.2 x BMR) were similar, while metabolic rates during plunge diving were much higher (ca. 47 x BMR). The proportion of the measurement interval spent foraging had a positive effect on FMR (R2 = 0.68), while the combined proportion of time engaged in nest attendance and loafing near the colony had a negative effect on FMR (R2 = 0.72). Thus, more than two-thirds of the variation in kittiwake FMR could be explained by the allocation of time among various activities. The high energetic cost of plunge diving relative to straight flight and searching flight suggests that kittiwakes can optimize their foraging strategy under conditions of low food availability by commuting long distances to feed in areas where gross foraging efficiency is high.

  12. Cardiovascular, Metabolic Effects and Dietary Composition of Ad-Libitum Paleolithic vs. Australian Guide to Healthy Eating Diets: A 4-Week Randomised Trial

    PubMed Central

    Genoni, Angela; Lyons-Wall, Philippa; Lo, Johnny; Devine, Amanda

    2016-01-01

    (1) Background: The Paleolithic diet is popular in Australia, however, limited literature surrounds the dietary pattern. Our primary aim was to compare the Paleolithic diet with the Australian Guide to Healthy Eating (AGHE) in terms of anthropometric, metabolic and cardiovascular risk factors, with a secondary aim to examine the macro and micronutrient composition of both dietary patterns; (2) Methods: 39 healthy women (mean ± SD age 47 ± 13 years, BMI 27 ± 4 kg/m2) were randomised to either the Paleolithic (n = 22) or AGHE diet (n = 17) for four weeks. Three-day weighed food records, body composition and biochemistry data were collected pre and post intervention; (3) Results: Significantly greater weight loss occurred in the Paleolithic group (−1.99 kg, 95% CI −2.9, −1.0), p < 0.001). There were no differences in cardiovascular and metabolic markers between groups. The Paleolithic group had lower intakes of carbohydrate (−14.63% of energy (E), 95% CI −19.5, −9.7), sodium (−1055 mg/day, 95% CI −1593, −518), calcium (−292 mg/day 95% CI −486.0, −99.0) and iodine (−47.9 μg/day, 95% CI −79.2, −16.5) and higher intakes of fat (9.39% of E, 95% CI 3.7, 15.1) and β-carotene (6777 μg/day 95% CI 2144, 11410) (all p < 0.01); (4) Conclusions: The Paleolithic diet induced greater changes in body composition over the short-term intervention, however, larger studies are recommended to assess the impact of the Paleolithic vs. AGHE diets on metabolic and cardiovascular risk factors in healthy populations. PMID:27223304

  13. Cardiovascular, Metabolic Effects and Dietary Composition of Ad-Libitum Paleolithic vs. Australian Guide to Healthy Eating Diets: A 4-Week Randomised Trial.

    PubMed

    Genoni, Angela; Lyons-Wall, Philippa; Lo, Johnny; Devine, Amanda

    2016-05-23

    (1) BACKGROUND: The Paleolithic diet is popular in Australia, however, limited literature surrounds the dietary pattern. Our primary aim was to compare the Paleolithic diet with the Australian Guide to Healthy Eating (AGHE) in terms of anthropometric, metabolic and cardiovascular risk factors, with a secondary aim to examine the macro and micronutrient composition of both dietary patterns; (2) METHODS: 39 healthy women (mean ± SD age 47 ± 13 years, BMI 27 ± 4 kg/m²) were randomised to either the Paleolithic (n = 22) or AGHE diet (n = 17) for four weeks. Three-day weighed food records, body composition and biochemistry data were collected pre and post intervention; (3) RESULTS: Significantly greater weight loss occurred in the Paleolithic group (-1.99 kg, 95% CI -2.9, -1.0), p < 0.001). There were no differences in cardiovascular and metabolic markers between groups. The Paleolithic group had lower intakes of carbohydrate (-14.63% of energy (E), 95% CI -19.5, -9.7), sodium (-1055 mg/day, 95% CI -1593, -518), calcium (-292 mg/day 95% CI -486.0, -99.0) and iodine (-47.9 μg/day, 95% CI -79.2, -16.5) and higher intakes of fat (9.39% of E, 95% CI 3.7, 15.1) and β-carotene (6777 μg/day 95% CI 2144, 11410) (all p < 0.01); (4) CONCLUSIONS: The Paleolithic diet induced greater changes in body composition over the short-term intervention, however, larger studies are recommended to assess the impact of the Paleolithic vs. AGHE diets on metabolic and cardiovascular risk factors in healthy populations.

  14. Temperature, field activity and post-feeding metabolic response in the Asian house gecko, Hemidactylus frenatus.

    PubMed

    Lei, Juan; Booth, David T

    2014-10-01

    Temperature has significant effects on physiological activities and geographical distribution of ectotherms. The Asian house gecko Hemidactylus frenatus has become one of the most widely distributed reptiles in the world and is an invasive species in Australia. Since being introduced into northern Australia, Asian house geckos have spread rapidly and expanded into south-east Queensland and northern New South Wales. Despite their rapid spread, there have been few studies that address thermal adaptability of this species. In order to understand how temperature might limit the distribution and feeding behavior of H. frenatus we observed gecko foraging activities in the wild over the winter period, measured the temperature at which voluntary feeding ceases, and assessed the effect of temperature (30, 25, 20, and 18 °C) on post-feeding metabolic rate. Resting metabolic rate and post-feeding peak in metabolic rate decreased with low temperature, while the duration of elevated metabolic rate after feeding increased at lower temperature. The SDA coefficient (a ratio of the energy expended due to the post-feeding rise in metabolic rate to the energy contained within the meal) did not change systematically with ambient temperature. Field observations and voluntary feeding experiments showed that H. frenatus stop feeding when ambient temperature drops below 17 °C, so that persistent night time temperatures below 17 °C may be limiting the distribution of this species.

  15. Simultaneous water activation and glucose metabolic rate imaging with PET

    NASA Astrophysics Data System (ADS)

    Verhaeghe, Jeroen; Reader, Andrew J.

    2013-02-01

    A novel imaging and signal separation strategy is proposed to be able to separate [18F]FDG and multiple [15O]H2O signals from a simultaneously acquired dynamic PET acquisition of the two tracers. The technique is based on the fact that the dynamics of the two tracers are very distinct. By adopting an appropriate bolus injection strategy and by defining tailored sets of basis functions that model either the FDG or water component, it is possible to separate the FDG and water signal. The basis functions are inspired from the spectral analysis description of dynamic PET studies and are defined as the convolution of estimated generating functions (GFs) with a set of decaying exponential functions. The GFs are estimated from the overall measured head curve, while the decaying exponential functions are pre-determined. In this work, the time activity curves (TACs) are modelled post-reconstruction but the model can be incorporated in a global 4D reconstruction strategy. Extensive PET simulation studies are performed considering single [18F]FDG and 6 [15O]H2O bolus injections for a total acquisition time of 75 min. The proposed method is evaluated at multiple noise levels and different parameters were estimated such as [18F]FDG uptake and blood flow estimated from the [15O]H2O component, requiring a full dynamic analysis of the two components, static images of [18F]FDG and the water components as well as [15O]H2O activation. It is shown that the resulting images and parametric values in ROIs are comparable to images obtained from separate imaging, illustrating the feasibility of simultaneous imaging of [18F]FDG and [15O]H2O components. For more information on this article, see medicalphysicsweb.org

  16. Isomaltulose Is Actively Metabolized in Plant Cells1

    PubMed Central

    Wu, Luguang; Birch, Robert G.

    2011-01-01

    Isomaltulose is a structural isomer of sucrose (Suc). It has been widely used as a nonmetabolized sugar in physiological studies aimed at better understanding the regulatory roles and transport of sugars in plants. It is increasingly used as a nutritional human food, with some beneficial properties including low glycemic index and acariogenicity. Cloning of genes for Suc isomerases opened the way for direct commercial production in plants. The understanding that plants lack catabolic capabilities for isomaltulose indicated a possibility of enhanced yields relative to Suc. However, this understanding was based primarily on the treatment of intact cells with exogenous isomaltulose. Here, we show that sugarcane (Saccharum interspecific hybrids), like other tested plants, does not readily import or catabolize extracellular isomaltulose. However, among intracellular enzymes, cytosolic Suc synthase (in the breakage direction) and vacuolar soluble acid invertase (SAI) substantially catabolize isomaltulose. From kinetic studies, the specificity constant of SAI for isomaltulose is about 10% of that for Suc. Activity varied against other Suc isomers, with Vmax for leucrose about 6-fold that for Suc. SAI activities from other plant species varied substantially in substrate specificity against Suc and its isomers. Therefore, in physiological studies, the blanket notion of Suc isomers including isomaltulose as nonmetabolized sugars must be discarded. For example, lysis of a few cells may result in the substantial hydrolysis of exogenous isomaltulose, with profound downstream signal effects. In plant biotechnology, different Vmax and Vmax/Km ratios for Suc isomers may yet be exploited, in combination with appropriate developmental expression and compartmentation, for enhanced sugar yields. PMID:22010106

  17. Polyphenols from Bee Pollen: Structure, Absorption, Metabolism and Biological Activity.

    PubMed

    Rzepecka-Stojko, Anna; Stojko, Jerzy; Kurek-Górecka, Anna; Górecki, Michał; Kabała-Dzik, Agata; Kubina, Robert; Moździerz, Aleksandra; Buszman, Ewa

    2015-12-04

    Bee pollen constitutes a natural source of antioxidants such as phenolic acids and flavonoids, which are responsible for its biological activity. Research has indicated the correlation between dietary polyphenols and cardioprotective, hepatoprotective, anti-inflammatory, antibacterial, anticancerogenic, immunostimulating, antianaemic effects, as well as their beneficial influence on osseous tissue. The beneficial effects of bee pollen on health result from the presence of phenolic acids and flavonoids which possess anti-inflammatory properties, phytosterol and linolenic acid which play an anticancerogenic role, and polysaccharides which stimulate immunological activity. Polyphenols are absorbed in the alimentary tract, metabolised by CYP450 enzymes, and excreted with urine and faeces. Flavonoids and phenolic acids are characterised by high antioxidative potential, which is closely related to their chemical structure. The high antioxidant potential of phenolic acids is due to the presence and location of hydroxyl groups, a carboxyl group in the immediate vicinity of ortho-diphenolic substituents, and the ethylene group between the phenyl ring and the carboxyl group. As regards flavonoids, essential structural elements are hydroxyl groups at the C5 and C7 positions in the A ring, and at the C3' and C4' positions in the B ring, and a hydroxyl group at the C3 position in the C ring. Furthermore, both, the double bond between C2 and C3, and a ketone group at the C4 position in the C ring enhance the antioxidative potential of these compounds. Polyphenols have an ideal chemical structure for scavenging free radicals and for creating chelates with metal ions, which makes them effective antioxidants in vivo.

  18. Probing for the Activities of Arsenic and Selenium Metabolizing Microbes

    NASA Astrophysics Data System (ADS)

    Stolz, J. F.

    2007-12-01

    Microbial activities can directly impact the mobility and toxicity of arsenic and selenium in the environment. Arsenic is cycled through oxidation/reduction and methylation/demethylation reactions as part of resistance and respiratory processes. The requirement for selenium is primarily for incorporation into selenocysteine and its function in selenoenzymes. Selenium oxyanions can also serve as an electron acceptor in anaerobic respiration. Both culture and culture-independent methods have been developed to detect the presence and activity of organisms capable of arsenic and selenium transformations. Enrichment media have been successful at cultivating arsenate respiring bacteria from a variety of environments, however, both electron donor and the concentration of arsenic can exert strong selective pressure. Thus, the organisms in the enrichment culture may not be the dominant organisms in the environment. Culture-independent methods, including immunological approaches (e.g., polyclonal antibodies to ArrA) and PCR-based technologies, have also had mixed success. PCR-primers designed to amplify portions of genes involved in resistance (e.g., arsC, acr3), respiration (e.g., arrA), and oxidation (e.g., aoxB) have been useful in several environments. Applications include T-RFLP, rt-PCR, and DGGE analyses. Nevertheless, these primers do not work with certain organisms suggesting the existence of additional enzymes and pathways. Although the biosynthetic pathway (and the proteins involved) for selenocysteine has been described in detail, much less is known about selenium methylation, assimilation and respiration. Only one respiratory selenate reductase has been characterized and its close sequence identity with chlorate and perchlorate reductases has complicated efforts to design a functional probe. Thus many aspects of the biogeochemical cycle of selenium remains to be explored.

  19. Salinity effects on viability, metabolic activity and proliferation of three Perkinsus species

    USGS Publications Warehouse

    La, Peyre M.; Casas, S.; La, Peyre J.

    2006-01-01

    Little is known regarding the range of conditions in which many Perkinsus species may proliferate, making it difficult to predict conditions favorable for their expansion, to identify conditions inducing mortality, or to identify instances of potential cross-infectivity among sympatric host species. In this study, the effects of salinity on viability, metabolic activity and proliferation of P. marinus, P. olseni and P. chesapeaki were determined. Specifically, this research examined the effects of 5 salinities (7, 11, 15, 25, 35???), (1) without acclimation, on the viability and metabolic activity of 2 isolates of each Perkinsus species, and (2) with acclimation, on the viability, metabolic activity, size and number of 1 isolate of each species. P. chesapeaki showed the widest range of salinity tolerance of the 3 species, with high viability and cell proliferation at all salinities tested. Although P. chesapeaki originated from low salinity areas (i.e. <15???), several measures (i.e. cell number and metabolic activity) indicated that higher salinities (15, 25???) were more favorable for its growth. P. olseni, originating from high salinity areas, had better viability and proliferation at the higher salinities (15, 25, 35???). Distinct differences in acute salinity response of the 2 P. olseni isolates at lower salinities (7, 11???), however, suggest the need for a more expansive comparison of isolates to better define the lower salinity tolerance. Lastly, P. marinus was more tolerant of the lower salinities (7 and 11???) than P. olseni, but exhibited reduced viability at 7???, even after acclimation. ?? Inter-Research 2006.

  20. Differential metabolic activity in the striosome and matrix compartments of the rat striatum during natural behaviors.

    PubMed

    Brown, Lucy L; Feldman, Samuel M; Smith, Diane M; Cavanaugh, James R; Ackermann, Robert F; Graybiel, Ann M

    2002-01-01

    The striosome and matrix compartments of the striatum are clearly identified by their neurochemical expression patterns and anatomical connections. To determine whether these compartments are distinguishable functionally, we used [14C]deoxyglucose metabolic mapping in the rat and tested whether neutral behavioral states (free movement, gentle restraint, and focal tactile stimulation under gentle restraint) were associated with regions of high metabolic activity in the matrix, in striosomes, or in both. We identified metabolic peaks in the striatum by means of image analysis, striosome-matrix boundaries by [3H]naloxone binding, and primary somatosensory corticostriatal input clusters by injections of anterograde tracer into electrophysiologically identified sites in SI. Peak metabolic activity was primarily confined to the matrix compartment under each behavioral condition. These findings show that during relatively neutral behavioral conditions the balance of activity between the two compartments favors the matrix and suggest that this balance is present in the striatum as part of normal behavior and processing of afferent activity.

  1. 5'-adenosine monophosphate-activated protein kinase and the metabolic syndrome.

    PubMed

    Mor, Vijay; Unnikrishnan, M K

    2011-09-01

    Lifestyle changes such as physical inactivity combined with calorie-rich, low-fibre diets have triggered an explosive surge in metabolic syndrome, outlined as a cluster of heart attack risk factors such as insulin resistance, raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. By acting as a master-switch of energy homeostasis and associated pathophysiological phenomena, 5'-adenosine monophosphate-activated protein kinase (AMPK) appears to orchestrate the adaptive physiology of energy deficit, suggesting that the sedentary modern human could be suffering from chronic suboptimal AMPK activation. Addressing individual targets with potent ligands with high specificity may be inappropriate (it has not yielded any molecule superior to the sixty year old metformin) because this strategy cannot address a cluster of interrelated pathologies. However, spices, dietary supplements and nutraceuticals attenuate the multiple symptoms of metabolic syndrome in a collective and perhaps more holistic fashion with fewer adverse events. Natural selection could have favoured races that developed a taste for spices and dietary supplements, most of which are not only antioxidants but also activators of AMPK. The review will outline the various biochemical mechanisms and pathophysiological consequences of AMPK activation involving the cluster of symptoms that embrace metabolic syndrome and beyond. Recent advances that integrate energy homeostasis with a number of overarching metabolic pathways and physiological phenomena, including inflammatory conditions, cell growth and development, malignancy, life span, and even extending into environmental millieu, as in obesity mediated by gut microflora and others will also be outlined.

  2. Effect of tributyltin (TBT) in the metabolic activity of TBT-resistant and sensitive estuarine bacteria.

    PubMed

    Cruz, Andreia; Oliveira, Vanessa; Baptista, Inês; Almeida, Adelaide; Cunha, Angela; Suzuki, Satoru; Mendo, Sónia

    2012-01-01

    The effect of tributyltin (TBT) on growth and metabolic activity of three estuarine bacteria with different TBT resistance profiles was investigated in an organic-rich culture medium (TSB) and in phosphate buffered saline (PBS) buffer. Exposure to TBT was assessed by determining its effect on growth (OD(600 nm) measurement), bacterial productivity (leucine incorporation), viability (CFU counts), aggregation and cell size (from Live/Dead analysis), ATP and NADH concentrations. TBT exposure resulted in decrease of bacterial density, cell size, and metabolic activity. In addition, cell aggregates were observed in the TBT-treated cultures. TBT strongly affected bacterial cell metabolism and seemed to exert an effect on its equilibrium, interfering with cell activity. Also, TBT toxicity was lower when cells were grown in TSB than in PBS, suggesting that a nutrient-rich growth medium can protect cells from TBT toxicity. This study contributes to our understanding of the TBT-resistant cell behavior reflected in its physiology and metabolic activity. This information is of utmost importance for further studies of TBT bioremediation.

  3. Synthesis and evaluation of atorvastatin esters as prodrugs metabolically activated by human carboxylesterases.

    PubMed

    Mizoi, Kenta; Takahashi, Masato; Haba, Masami; Hosokawa, Masakiyo

    2016-02-01

    We synthesized 11 kinds of prodrug with an esterified carboxylic acid moiety of atorvastatin in moderate to high yields. We discovered that they underwent metabolic activation specifically by the human carboxylesterase 1 (CES1) isozyme. The results suggested that these ester compounds of atorvastatin have the potential to act as prodrugs in vivo.

  4. Metabolic Myopathies and Physical Activity: When Fatigue Is More Than Simple Exertion.

    ERIC Educational Resources Information Center

    Tarnopolsky, Mark A.

    2002-01-01

    When patients experience fatigue and muscle cramps beyond exercise adaptation, physicians should consider metabolic myopathies. The most common conditions seen in active patients are myoadenylate deaminase deficiency and disorders such as McArdle's disease. Targeted family histories and basic laboratory studies help rule out conditions mimicking…

  5. Biotransformation of anthelmintics and the activity of drug-metabolizing enzymes in the tapeworm Moniezia expansa.

    PubMed

    Prchal, Lukáš; Bártíková, Hana; Bečanová, Aneta; Jirásko, Robert; Vokřál, Ivan; Stuchlíková, Lucie; Skálová, Lenka; Kubíček, Vladimír; Lamka, Jiří; Trejtnar, František; Szotáková, Barbora

    2015-04-01

    The sheep tapeworm Moniezia expansa is very common parasite, which affects ruminants such as sheep, goats as well as other species. The benzimidazole anthelmintics albendazole (ABZ), flubendazole (FLU) and mebendazole (MBZ) are often used to treat the infection. The drug-metabolizing enzymes of helminths may alter the potency of anthelmintic treatment. The aim of our study was to assess the activity of the main drug-metabolizing enzymes and evaluate the metabolism of selected anthelmintics (ABZ, MBZ and FLU) in M. expansa. Activities of biotransformation enzymes were determined in subcellular fractions. Metabolites of the anthelmintics were detected and identified using high performance liquid chromatography/ultra-violet/VIS/fluorescence or ultra-high performance liquid chromatography/mass spectrometry. Reduction of MBZ, FLU and oxidation of ABZ were proved as well as activities of various metabolizing enzymes. Despite the fact that the conjugation enzymes glutathione S-transferase, UDP-glucuronosyl transferase and UDP-glucosyl transferase were active in vitro, no conjugated metabolites of anthelmintics were identified either ex vivo or in vitro. The obtained results indicate that sheep tapeworm is able to deactivate the administered anthelmintics, and thus protects itself against their action.

  6. Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative

    SciTech Connect

    Fernandez, J.P.; Robbe, Y.; Chapat, J.P.; Chanal, J.L.; Genin, M.; Sentenac-Roumanou, H.; Fatome, M.

    1983-09-01

    Molecular biotransformation of 2-phenylthiazolidine (1) and its m-bromo derivative (2) in the mouse is followed by autoradiographic studies and assessed by analysis of urinary metabolites. Cysteamine (4) is one of the metabolites of compounds 1 and 2. Radioprotective activity and efficacy over a period of time of 1, 2, and 4 correlate closely with distribution and metabolism.

  7. Peroxisome Proliferator Activated Receptor A Ligands as Anticancer Drugs Targeting Mitochondrial Metabolism

    PubMed Central

    Grabacka, Maja; Pierzchalska, Malgorzata; Reiss, Krzysztof

    2011-01-01

    Tumor cells show metabolic features distinctive from normal tissues, with characteristically enhanced aerobic glycolysis, glutaminolysis and lipid synthesis. Peroxisome proliferator activated receptor α (PPAR α) is activated by nutrients (fatty acids and their derivatives) and influences these metabolic pathways acting antagonistically to oncogenic Akt and c-Myc. Therefore PPAR α can be regarded as a candidate target molecule in supplementary anticancer pharmacotherapy as well as dietary therapeutic approach. This idea is based on hitting the cancer cell metabolic weak points through PPAR α mediated stimulation of mitochondrial fatty acid oxidation and ketogenesis with simultaneous reduction of glucose and glutamine consumption. PPAR α activity is induced by fasting and its molecular consequences overlap with the effects of calorie restriction and ketogenic diet (CRKD). CRKD induces increase of NAD+/NADH ratio and drop in ATP/AMP ratio. The first one is the main stimulus for enhanced protein deacetylase SIRT1 activity; the second one activates AMP-dependent protein kinase (AMPK). Both SIRT1 and AMPK exert their major metabolic activities such as fatty acid oxidation and block of glycolysis and protein, nucleotide and fatty acid synthesis through the effector protein peroxisome proliferator activated receptor gamma 1 α coactivator (PGC-1α). PGC-1α cooperates with PPAR α and their activities might contribute to potential anticancer effects of CRKD, which were reported for various brain tumors. Therefore, PPAR α activation can engage molecular interplay among SIRT1, AMPK, and PGC-1α that provides a new, low toxicity dietary approach supplementing traditional anticancer regimen. PMID:21133850

  8. AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases

    PubMed Central

    Srivastava, Rai Ajit K.; Pinkosky, Stephen L.; Filippov, Sergey; Hanselman, Jeffrey C.; Cramer, Clay T.; Newton, Roger S.

    2012-01-01

    The adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor of energy metabolism at the cellular as well as whole-body level. It is activated by low energy status that triggers a switch from ATP-consuming anabolic pathways to ATP-producing catabolic pathways. AMPK is involved in a wide range of biological activities that normalizes lipid, glucose, and energy imbalances. These pathways are dysregulated in patients with metabolic syndrome (MetS), which represents a clustering of major cardiovascular risk factors including diabetes, lipid abnormalities, and energy imbalances. Clearly, there is an unmet medical need to find a molecule to treat alarming number of patients with MetS. AMPK, with multifaceted activities in various tissues, has emerged as an attractive drug target to manage lipid and glucose abnormalities and maintain energy homeostasis. A number of AMPK activators have been tested in preclinical models, but many of them have yet to reach to the clinic. This review focuses on the structure-function and role of AMPK in lipid, carbohydrate, and energy metabolism. The mode of action of AMPK activators, mechanism of anti-inflammatory activities, and preclinical and clinical findings as well as future prospects of AMPK as a drug target in treating cardio-metabolic disease are discussed. PMID:22798688

  9. Sympathetic nervous activation in obesity and the metabolic syndrome--causes, consequences and therapeutic implications.

    PubMed

    Lambert, Gavin W; Straznicky, Nora E; Lambert, Elisabeth A; Dixon, John B; Schlaich, Markus P

    2010-05-01

    The world wide prevalence of obesity and the metabolic syndrome is escalating. Contrary to earlier experimental evidence, human obesity is characterised by sympathetic nervous activation, with the outflows to both the kidney and skeletal muscle being activated. While the mechanisms responsible for initiating the sympathetic activation remain to be unequivocally elucidated, hyperinsulinemia, obstructive sleep apnoea, increased circulating adipokines, stress and beta adrenergic receptor polymorphisms are implicated. The pattern of sympathetic activation may be the pathophysiological mechanism underpinning much obesity-related illnesses with the consequences including, amongst others, the development of hypertension, insulin resistance, diastolic dysfunction and renal impairment. While diet and exercise are the first line therapy for the treatment of obesity and the metabolic syndrome, pharmacological interventions targeting the sympathetic nervous system, either directly or indirectly are also likely to be of benefit. Importantly, the benefit may not necessarily be weight related but may be associated with a reduction in end organ damage.

  10. DMPP-added nitrogen fertilizer affects soil N2O emission and microbial activity in Southern Italy

    NASA Astrophysics Data System (ADS)

    Vitale, Luca; De Marco, Anna; Maglione, Giuseppe; Polimeno, Franca; Di Tommasi, Paul; Magliulo, Vincenzo

    2014-05-01

    Arable sites contributes to global N2O emission due to massive utilization of nitrogen fertilizers. N2O derives from the biological processes such as nitrification and denitrification influenced by soil nitrogen availability. The use of nitrogen fertilizers added with nitrification inhibitors represents one among the proposed strategy to reduce soil N2O emission form arable sites. The aim of this work was to evaluate the effects of 3,4-dimethylphyrazole phosphate (DMPP), a nitrification inhibitor, on N2O emission and microbial activity of a soil cropped to potato in Southern Italy. The experiment was a randomized block design with two treatments applied and three replicates: control (C) and DMPP (Entec®, K+S Nitrogen) plots, both supplied with the same amount of ammonium nitrate. The nitrogen fertilizer was supplied in three events: at 0 Day After Sowing (DAS; 100 kg N ha-1), at 57 DAS (30 kg N ha-1), and at 71 DAS (30 kg N ha-1). Soil N2O emission was monitored by both dynamic and static chambers. Static chambers were located both on hills and furrows whereas dynamic chambers were located on furrows. Air samples were collected from chambers at different times and analysed by a gas chromatograph (SRI 8610C, Gas Chromatograph). Fluxes were estimated as a linear interpolation of N2O changes over a 30 min time. Microbial biomass and basal respiration were determined as CO2 evolution, analysed by means of an IRGA (Li6200, Licor), on 2 g of fresh soil over a 4h incubation time. Microbial biomass was determined by Substrate Induced Respiration method. Data show no statistical differences in N2O fluxes measured with either dynamic chambers between C and DMPP plots in studied period. However, after the first fertilization event, when the fertilizer was applied as 100 kg N ha-1, the average N2O fluxes measured with static chambers were higher in DMPP plots compared to C plots. In the same period, the microbial biomass significantly decreased in DMPP plots as compared to C

  11. Direct thyroid hormone activation of mitochondria: identification of adenine nucleotide translocase (AdNT) as the hormone receptor.

    PubMed

    Sterling, K

    1987-01-01

    Earlier we presented preliminary data suggesting that the thyroid hormone triiodothyronine (T3) is bound with an association constant (Ka) approximating 2 X 10(11) M-1 by the ADP/ATP carrier, adenine nucleotide translocase (AdNT) purified from beef heart mitochondria (Endocrinology 110: 292, 1986). We now report that [125I] T3 is capable of photoaffinity labeling not only purified AdNT but also the carrier in intact beef heart mitochondria. The identity of the covalently labeled AdNT was corroborated by two dimensional electrophoresis (O'Farrell) with pI approximately 10 on electrofocusing (first dimension) and Mr approximately 31,000 on SDS gel (second dimension). Further identification of the covalently labeled material as authentic AdNT was afforded by recognition by specific monoclonal antibodies. Moreover, we found that addition of excess nonradioactive T3 to intact mitochondria or to mitochondrial protein solution prior to photoaffinity labeling resulted in inhibition of formation of labeled AdNT, compatible with saturation of limited capacity binding sites rather than nonspecific labeling with the ligand [125I] T3. It was considered highly significant that labeling in intact mitochondria was at least an order of magnitude greater than that observed with purified AdNT. This finding is compatible with our concept of an important role of the lipid microenvironment in the intact mitochondrial membrane in T3 binding.

  12. Fatty acid metabolic reprogramming via mTOR-mediated inductions of PPARγ directs early activation of T cells

    PubMed Central

    Angela, Mulki; Endo, Yusuke; Asou, Hikari K.; Yamamoto, Takeshi; Tumes, Damon J.; Tokuyama, Hirotake; Yokote, Koutaro; Nakayama, Toshinori

    2016-01-01

    To fulfil the bioenergetic requirements for increased cell size and clonal expansion, activated T cells reprogramme their metabolic signatures from energetically quiescent to activated. However, the molecular mechanisms and essential components controlling metabolic reprogramming in T cells are not well understood. Here, we show that the mTORC1–PPARγ pathway is crucial for the fatty acid uptake programme in activated CD4+ T cells. This pathway is required for full activation and rapid proliferation of naive and memory CD4+ T cells. PPARγ directly binds and induces genes associated with fatty acid uptake in CD4+ T cells in both mice and humans. The PPARγ-dependent fatty acid uptake programme is critical for metabolic reprogramming. Thus, we provide important mechanistic insights into the metabolic reprogramming mechanisms that govern the expression of key enzymes, fatty acid metabolism and the acquisition of an activated phenotype during CD4+ T cell activation. PMID:27901044

  13. Alternate radiolabeled markers for detecting metabolic activity of Mycobacterium leprae residing in murine macrophages

    SciTech Connect

    Prasad, H.K.; Hastings, R.C.

    1985-05-01

    This study demonstrated the utility of using 4% NaOH as a murine macrophage cell-solubilizing agent to discriminate between host macrophage metabolism and that of intracellular Mycobacterium leprae. A 4% concentration of NaOH had no deleterious effect on labeled mycobacteria. Thereby, alternate radiolabeled indicators of the metabolic activity of intracellular M. leprae could be experimented with. Significant incorporation of /sup 14/C-amino acid mixture, (/sup 14/C)leucine, (/sup 14/C)uridine, and carrier-free /sup 32/P was observed in cultures containing freshly extracted (''live'') strains of M. leprae as compared with control cultures containing autoclaved bacilli.

  14. Homocysteine Activates B Cells via Regulating PKM2-Dependent Metabolic Reprogramming

    PubMed Central

    Deng, Jiacheng; Lü, Silin; Liu, Huiying; Liu, Bo; Jiang, Changtao; Xu, Qingbo

    2017-01-01

    The overactivation of immune cells plays an important role in the pathogenesis of hyperhomocysteinemia (HHcy)-accelerated atherosclerosis. Homocysteine (Hcy) activates B cell proliferation and Ab secretion; however, the underlying mechanisms for these effects remain largely unknown. Metabolic reprogramming is critical for lymphocyte activation and effector function. In this study, we showed that Hcy-activated B cells displayed an increase in both oxidative phosphorylation and glycolysis, with a tendency to shift toward the latter, as well as an accumulation of intermediates in the pentose phosphate pathway, to provide energy and biosynthetic substrates for cell growth and function. Mechanistically, Hcy increased both the protein expression and glycolytic enzyme activity of the pyruvate kinase muscle isozyme 2 (PKM2) in B cells, whereas the PKM2 inhibitor shikonin restored Hcy-induced metabolic changes, as well as B cell proliferation and Ab secretion both in vivo and in vitro, indicating that PKM2 plays a critical role in metabolic reprogramming in Hcy-activated B cells. Further investigation revealed that the Akt–mechanistic target of rapamycin signaling pathway was involved in this process, as the mechanistic target of rapamycin inhibitor rapamycin inhibited Hcy-induced changes in PKM2 enzyme activity and B cell activation. Notably, shikonin treatment effectively attenuated HHcy-accelerated atherosclerotic lesion formation in apolipoprotein E–deficient mice. In conclusion, our results demonstrate that PKM2 is required to support metabolic reprogramming for Hcy-induced B cell activation and function, and it might serve as a critical regulator in HHcy-accelerated initiation of atherosclerosis. PMID:27903739

  15. Physical activity is associated with retained muscle metabolism in human myotubes challenged with palmitate.

    PubMed

    Green, C J; Bunprajun, T; Pedersen, B K; Scheele, C

    2013-09-15

      The aim of this study was to investigate whether physical activity is associated with preserved muscle metabolism in human myotubes challenged with saturated fatty acids. Human muscle satellite cells were isolated from sedentary or active individuals and differentiated into myocytes in culture. Metabolic differences were then investigated in the basal state or after chronic palmitate treatment. At basal, myocytes from sedentary individuals exhibited higher CD36 and HSP70 protein expression as well as elevated phosphorylation of c-Jun NH2-terminal kinase (JNK) and insulin receptor substrate 1 (IRS1) serine(307) compared to myocytes from active individuals. Despite equal lipid accumulation following palmitate treatment, myocytes from sedentary individuals exhibited delayed acetyl coenzyme A carboxylase phosphorylation compared to the active group. Myocytes from sedentary individuals had significantly higher basal glucose uptake and palmitate promoted insulin resistance in sedentary myocytes. Importantly, myocytes from active individuals were partially protected from palmitate-induced insulin resistance. Palmitate treatment enhanced IRS1 serine307 phosphorylation in myocytes from sedentary individuals and correlated positively to JNK phosphorylation. In conclusion, muscle satellite cells retain metabolic differences associated with physical activity. Physical activity partially protects myocytes from fatty acid-induced insulin resistance and inactivity is associated with dysregulation of metabolism in satellite cells challenged with palmitate. Although the benefits of physical activity on whole body physiology have been well investigated, this paper presents novel findings that both diet and exercise impact satellite cells directly. Given the fact that satellite cells are important for muscle maintenance, a dysregulated function could have profound effects on health. Therefore the effects of lifestyle on satellite cells needs to be delineated.

  16. Promutagen activation of triazine herbicides metribuzin and ametryn through Vicia faba metabolism inducing sister chromatid exchanges in human lymphocytes in vitro and in V. faba root tip meristems.

    PubMed

    Flores-Maya, Saúl; Gómez-Arroyo, Sandra; Calderón-Segura, María Elena; Villalobos-Pietrini, Rafael; Waliszewski, Stefan M; de la Cruz, Leticia Gómez

    2005-03-01

    The aim of our study was the induction of sister chromatid exchanges (SCE) in human lymphocytes in vitro and in root tip meristems of Vicia faba to evaluate the genotoxic effects of metribuzin and ametryn. Direct treatments of these herbicides on human lymphocytes in vitro applied 24 h after the beginning of culture did not induce SCE; however, they showed a cytotoxic effect in the cultures expressed as cellular death. On the contrary, when extracts of V. faba roots, treated for 4 h with metribuzin and ametryn (in vivo activation), were added to the lymphocyte cultures, SCEs were significantly induced with an asymptotic response. Negative responses appeared with the in vitro assays, in which metribuzin and ametryn were added directly to the 48 h lymphocyte cultures for 4 h. Nevertheless, in treatments in which the S10 metabolic mix was added, the SCE frequencies were significantly different to the control, although a concentration-response relationship was only observed with metribuzin. The results showed that both herbicides needed the V. faba metabolism to produce SCE in human lymphocyte cultures. Metribuzin and ametryn applied to V. faba root tip meristems for 4 h increased SCE frequency significantly, and a concentration-response relationship was observed with both herbicides.

  17. Assessing microbial communities for a metabolic profile similar to activated sludge.

    PubMed

    Paixão, S M; Sàágua, M C; Tenreiro, R; Anselmo, A M

    2007-05-01

    To search for reliable testing inocula alternatives to activated sludge cultures, several model microbial consortia were compared with activated sludge populations for their functional diversity. The evaluation of the metabolic potential of these mixed inocula was performed using the Biolog EcoPlates and GN and GP MicroPlates (Biolog, Inc., Hayward, California). The community-level physiological profiles (CLPPs) obtained for model communities and activated sludge samples were analyzed by principal component analysis and hierarchic clustering methods, to evaluate the ability of Biolog plates to distinguish among the different microbial communities. The effect of different inocula preparation methodologies on the community structure was also studied. The CLPPs obtained with EcoPlates and GN MicroPlates showed that EcoPlates are suitable to screen communities with a metabolic profile similar to activated sludge. New, well-defined, standardized, and safe inocula presenting the same metabolic community profile as activated sludge were selected and can be tested as surrogate cultures in activated-sludge-based bioassays.

  18. [Effect of copper pollution on seedling growth and activate oxygen metabolism of Trifolium pratense].

    PubMed

    Chu, Ling; Liu, Dengyi; Wang, Youbao; Li, Ying; Liu, Huijun

    2004-01-01

    The effect of copper (Cu) pollution on the seedling growth and activate oxygen metabolism of Trifolium pratense was studied by water cultivation experiments. The results showed that under low concentration of Cu (< 10 mg.L-1), the growth of Trifolium pratense seedlings could be improved, their fresh/dry weight and the contents of soluble protein and chlorophylls in leaves increased slightly, the MDA content of leaf cells decreased, the activities of SOD, CAT and POD in the activate oxygen metabolism system slightly increased, and the balance of protective enzyme system was hold. However, with the increase of Cu concentration (10-100 mg.L-1), there existed an obvious negative effect on the growth of Trifolium pratense seedlings. The seedlings under high concentrations of Cu were shorter and smaller, their fibrous roots were shorter and fewer, and their fresh/dry weight and the contents of soluble protein and chlorophylls in leaves decreased drastically. With the increase of Cu concentration, the membrane penetration, electric conductivity and MDA content of leaf cells increased. Furthermore, the activate oxygen metabolism system was destroyed, the balance of protective enzyme system was broken, the activities of SOD and CAT decreased by 26.67% and 71.31%, respectively, while the POD activity increased by 10.6 times.

  19. Seasonal changes in thermal environment and metabolic enzyme activity in the diamondback terrapin (Malaclemys terrapin).

    PubMed

    Williard, Amanda Southwood; Harden, Leigh Anne

    2011-04-01

    Diamondback terrapins experience broad fluctuations in temperature on both a daily and seasonal basis in their estuarine environment. We measured metabolic enzyme activity in terrapin muscle tissue to assess thermal dependence and the role of temperature in seasonal metabolic downregulation in this species. Activity of lactate dehydrogenase (LDH), pyruvate kinase (PK), citrate synthase (CS), and cytochrome c oxidase (CCO) was assayed at 10, 20, 30, and 40 °C for tissue collected during summer and winter. The Q(10) for enzyme activity varied between 1.31 and 2.11 within the temperature range at which terrapins were active (20-40 °C). The Q(10) for LDH, CS, and CCO varied between 1.39 and 1.76 and between 10 and 20 °C, but PK exhibited heightened thermal sensitivity within this lower temperature range, with a Q(10) of 2.90 for summer-collected tissue and 5.55 for winter-collected tissue. There was no significant effect of season on activity of LDH or PK, but activity of CS and CCO was significantly lower in winter-collected tissue compared with summer-collected tissue. Results indicate that temperature effects contribute to seasonal metabolic downregulation and dormancy in terrapins, but other environmental factors (i.e. oxygen availability), as well as seasonal shifts in blood biochemistry and circulating hormones may also play an important role.

  20. Anaerobic central metabolic pathways active during polyhydroxyalkanoate production in uncultured cluster 1 Defluviicoccus enriched in activated sludge communities.

    PubMed

    Burow, Luke C; Mabbett, Amanda N; Borrás, Luis; Blackall, Linda L

    2009-09-01

    A glycogen nonpolyphosphate-accumulating organism (GAO) enrichment culture dominated by the Alphaproteobacteria cluster 1 Defluviicoccus was investigated to determine the metabolic pathways involved in the anaerobic formation of polyhydroxyalkanoates, carbon storage polymers important for the proliferation of microorganisms in enhanced biological phosphorus removal processes. FISH-microautoradiography and post-FISH fluorescent chemical staining confirmed acetate assimilation as polyhydroxyalkanoates in cluster 1 Defluviicoccus under anaerobic conditions. Chemical inhibition of glycolysis using iodoacetate, and of isocitrate lyase by 3-nitropropionate and itaconate, indicated that carbon is likely to be channelled through both glycolysis and the glyoxylate cycle in cluster 1 Defluviicoccus. The effect of metabolic inhibitors of aconitase (monofluoroacetate) and succinate dehydrogenase (malonate) suggested that aconitase, but not succinate dehydrogenase, was active, providing further support for the role of the glyoxylate cycle in these GAOs. Metabolic inhibition of fumarate reductase using oxantel decreased polyhydroxyalkanoate production. This indicated reduction of fumarate to succinate and the operation of the reductive branch of the tricarboxylic acid cycle, which is possibly important in the production of the polyhydroxyvalerate component of polyhydroxyalkanoates observed in cluster 1 Defluviicoccus enrichment cultures. These findings were integrated with previous metabolic models for GAOs and enabled an anaerobic central metabolic pathway model for polyhydroxyalkanoate formation in cluster 1 Defluviicoccus to be proposed.

  1. Metabolic inhibition enhances Ca(2+)-activated K+ current in smooth muscle cells of rabbit portal vein.

    PubMed

    Miller, A L; Morales, E; Leblanc, N R; Cole, W C

    1993-12-01

    The effect of metabolic inhibition on macroscopic and single-channel K+ currents in isolated rabbit portal vein myocytes was investigated by patch-clamp technique. Depression of adenosine triphosphate synthesis was produced by 2-deoxy-D-glucose (10 mM) and either cyanide (2 mM) or dinitrophenol (50 microM). Outward quasi-steady-state current evoked by a ramp protocol and outward time-dependent current during step depolarizations were increased during metabolic inhibition. The reversal potential for quasi-steady-state current shifted negatively toward equilibrium potential of K+ during treatment consistent with a role for K+ conductance and hyperpolarization of membrane potential. The macroscopic K+ current affected was 1) voltage dependent, 2) inhibited by intracellular Ca2+ chelation and low tetraethylammonium ion (1 mM) but unaffected by 4-aminopyridine (2 mM), and 3) associated with a rise in intracellular Ca2+ assessed by indo 1. Metabolic inhibition caused an increase in voltage-dependent large-conductance K+ channel (120-130 pS) activity in cell-attached patches of myocytes bathed in physiological solution (140 mM K+ in pipette). The channels were blocked in a flickery fashion by tetraethylammonium ion (0.5 mM) and inhibited with charybdotoxin (100 nM). We conclude that metabolic inhibition increases the activity of large-conductance Ca(2+)-activated K+ channels in vascular smooth muscle.

  2. Consistent abnormalities in metabolic network activity in idiopathic rapid eye movement sleep behaviour disorder.

    PubMed

    Wu, Ping; Yu, Huan; Peng, Shichun; Dauvilliers, Yves; Wang, Jian; Ge, Jingjie; Zhang, Huiwei; Eidelberg, David; Ma, Yilong; Zuo, Chuantao

    2014-12-01

    Rapid eye movement sleep behaviour disorder has been evaluated using Parkinson's disease-related metabolic network. It is unknown whether this disorder is itself associated with a unique metabolic network. 18F-fluorodeoxyglucose positron emission tomography was performed in 21 patients (age 65.0±5.6 years) with idiopathic rapid eye movement sleep behaviour disorder and 21 age/gender-matched healthy control subjects (age 62.5±7.5 years) to identify a disease-related pattern and examine its evolution in 21 hemi-parkinsonian patients (age 62.6±5.0 years) and 16 moderate parkinsonian patients (age 56.9±12.2 years). We identified a rapid eye movement sleep behaviour disorder-related metabolic network characterized by increased activity in pons, thalamus, medial frontal and sensorimotor areas, hippocampus, supramarginal and inferior temporal gyri, and posterior cerebellum, with decreased activity in occipital and superior temporal regions. Compared to the healthy control subjects, network expressions were elevated (P<0.0001) in the patients with this disorder and in the parkinsonian cohorts but decreased with disease progression. Parkinson's disease-related network activity was also elevated (P<0.0001) in the patients with rapid eye movement sleep behaviour disorder but lower than in the hemi-parkinsonian cohort. Abnormal metabolic networks may provide markers of idiopathic rapid eye movement sleep behaviour disorder to identify those at higher risk to develop neurodegenerative parkinsonism.

  3. MFN1 deacetylation activates adaptive mitochondrial fusion and protects metabolically challenged mitochondria.

    PubMed

    Lee, Joo-Yong; Kapur, Meghan; Li, Ming; Choi, Moon-Chang; Choi, Sujin; Kim, Hak-June; Kim, Inhye; Lee, Eunji; Taylor, J Paul; Yao, Tso-Pang

    2014-11-15

    Fasting and glucose shortage activate a metabolic switch that shifts more energy production to mitochondria. This metabolic adaptation ensures energy supply, but also elevates the risk of mitochondrial oxidative damage. Here, we present evidence that metabolically challenged mitochondria undergo active fusion to suppress oxidative stress. In response to glucose starvation, mitofusin 1 (MFN1) becomes associated with the protein deacetylase HDAC6. This interaction leads to MFN1 deacetylation and activation, promoting mitochondrial fusion. Deficiency in HDAC6 or MFN1 prevents mitochondrial fusion induced by glucose deprivation. Unexpectedly, failure to undergo fusion does not acutely affect mitochondrial adaptive energy production; instead, it causes excessive production of mitochondrial reactive oxygen species and oxidative damage, a defect suppressed by an acetylation-resistant MFN1 mutant. In mice subjected to fasting, skeletal muscle mitochondria undergo dramatic fusion. Remarkably, fasting-induced mitochondrial fusion is abrogated in HDAC6-knockout mice, resulting in extensive mitochondrial degeneration. These findings show that adaptive mitochondrial fusion protects metabolically challenged mitochondria.

  4. Plasticity in body temperature and metabolic capacity sustains winter activity in a small endotherm (Rattus fuscipes).

    PubMed

    Glanville, Elsa J; Seebacher, Frank

    2010-03-01

    Small mammals that remain active throughout the year at a constant body temperature have a much greater energy and food requirement in winter. Lower body temperatures in winter may offset the increased energetic cost of remaining active in the cold, if cellular metabolism is not constrained by a negative thermodynamic effect. We aimed to determine whether variable body temperatures can be advantageous for small endotherms by testing the hypothesis that body temperature fluctuates seasonally in a wild rat (Rattus fuscipes); conferring an energy saving and reducing food requirements during resource restricted winter. Additionally we tested whether changes in body temperature affected tissue specific metabolic capacity. Winter acclimatized rats had significantly lower body temperatures and thicker fur than summer acclimatized rats. Mitochondrial oxygen consumption and the activity of enzymes that control oxidative (citrate synthase, cytochrome c-oxidase) and anaerobic (lactate dehydrogenase) metabolism were elevated in winter and were not negatively affected by the lower body temperature. Energy transfer modeling showed that lower body temperatures in winter combined with increased fur thickness to confer a 25 kJ day(-1) energy saving, with up to 50% owing to reduced body temperature alone. We show that phenotypic plasticity at multiple levels of organization is an important component of the response of a small endotherm to winter. Mitochondrial function compensates for lower winter body temperatures, buffering metabolic heat production capacity.

  5. AMP-Activated Protein Kinase Regulates Oxidative Metabolism in Caenorhabditis elegans through the NHR-49 and MDT-15 Transcriptional Regulators

    PubMed Central

    Moreno-Arriola, Elizabeth; EL Hafidi, Mohammed; Ortega-Cuéllar, Daniel; Carvajal, Karla

    2016-01-01

    Cellular energy regulation relies on complex signaling pathways that respond to fuel availability and metabolic demands. Dysregulation of these networks is implicated in the development of human metabolic diseases such as obesity and metabolic syndrome. In Caenorhabditis elegans the AMP-activated protein kinase, AAK, has been associated with longevity and stress resistance; nevertheless its precise role in energy metabolism remains elusive. In the present study, we find an evolutionary conserved role of AAK in oxidative metabolism. Similar to mammals, AAK is activated by AICAR and metformin and leads to increased glycolytic and oxidative metabolic fluxes evidenced by an increase in lactate levels and mitochondrial oxygen consumption and a decrease in total fatty acids and lipid storage, whereas augmented glucose availability has the opposite effects. We found that these changes were largely dependent on the catalytic subunit AAK-2, since the aak-2 null strain lost the observed metabolic actions. Further results demonstrate that the effects due to AAK activation are associated to SBP-1 and NHR-49 transcriptional factors and MDT-15 transcriptional co-activator, suggesting a regulatory pathway that controls oxidative metabolism. Our findings establish C. elegans as a tractable model system to dissect the relationship between distinct molecules that play a critical role in the regulation of energy metabolism in human metabolic diseases. PMID:26824904

  6. Benzene metabolism by human liver microsomes in relation to cytochrome P450 2E1 activity.

    PubMed

    Seaton, M J; Schlosser, P M; Bond, J A; Medinsky, M A

    1994-09-01

    Low levels of benzene from sources including cigarette smoke and automobile emissions are ubiquitous in the environment. Since the toxicity of benzene probably results from oxidative metabolites, an understanding of the profile of biotransformation of low levels of benzene is critical in making a valid risk assessment. To that end, we have investigated metabolism of a low concentration of [14C]benzene (3.4 microM) by microsomes from human, mouse and rat liver. The extent of phase I benzene metabolism by microsomal preparations from 10 human liver samples and single microsomal preparations from both mice and rats was then related to measured activities of cytochrome P450 (CYP) 2E1. Measured CYP 2E1 activities, as determined by hydroxylation of p-nitrophenol, varied 13-fold (0.253-3.266 nmol/min/mg) for human samples. The fraction of benzene metabolized in 16 min ranged from 10% to 59%. Also at 16 min, significant amounts of oxidative metabolites were formed. Phenol was the main metabolite formed by all but two human microsomal preparations. In those samples, both of which had high CYP 2E1 activity, hydroquinone was the major metabolite formed. Both hydroquinone and catechol formation showed a direct correlation with CYP 2E1 activity over the range of activities present. A simulation model was developed based on a mechanism of competitive inhibition between benzene and its oxidized metabolites, and was fit to time-course data for three human liver preparations. Model calculations for initial rates of benzene metabolism ranging from 0.344 to 4.442 nmol/mg/min are directly proportional to measured CYP 2E1 activities. The model predicted the dependence of benzene metabolism on the measured CYP 2E1 activity in human liver samples, as well as in mouse and rat liver samples. These results suggest that differences in measured hepatic CYP 2E1 activity may be a major factor contributing to both interindividual and interspecies variations in hepatic metabolism of benzene

  7. Susceptibility of Candida albicans biofilms to caspofungin and anidulafungin is not affected by metabolic activity or biomass production.

    PubMed

    Marcos-Zambrano, Laura Judith; Escribano, Pilar; Bouza, Emilio; Guinea, Jesús

    2016-02-01

    Micafungin is more active against biofilms with high metabolic activity; however, it is unknown whether this observation applies to caspofungin and anidulafungin and whether it is also dependent on the biomass production. We compare the antifungal activity of anidulafungin, caspofungin, and micafungin against preformed Candida albicans biofilms with different degrees of metabolic activity and biomass production from 301 isolates causing fungemia in patients admitted to Gregorio Marañon Hospital (January 2007 to September 2014). Biofilms were classified as having low, moderate, or high metabolic activity according XTT reduction assay or having low, moderate, or high biomass according to crystal violet assay. Echinocandin MICs for planktonic and sessile cells were measured using the EUCAST E.Def 7.2 procedure and XTT reduction assay, respectively. Micafungin showed the highest activity against biofilms classified according to the metabolic activity and biomass production (P < .001). The activity of caspofungin and anidulafungin was not dependent on the metabolic activity of the biofilm or the biomass production. These observations were confirmed by scanning electron microscopy. None of the echinocandins produced major changes in the structure of biofilms with low metabolic activity and biomass production when compared with the untreated biofilms. However, biofilm with high metabolic activity or high biomass production was considerably more susceptible to micafungin; this effect was not shown by caspofungin or anidulafungin.

  8. Chromospherically active stars. 12: ADS 11060 C: A double lined K dwarf binary in a quintuple system

    NASA Technical Reports Server (NTRS)

    Fekel, Francis C.; Henry, Gregory W.; Hampton, Melissa L.; Fried, Robert; Morton, Mary D.

    1994-01-01

    ADS 11060 C is a double lined spectroscopic binary with a period of 25.7631 days and an eccentricity of 0.565. Spectral types of the two stars are estimated as K7 V and MO V with a magnitude difference of about 0.55 mag in V. The stars appear to be somewhat metal rich with respect to the Sun. Despite the relatively large masses of 0.53 and 0.51 solar mass, our photometric observations find no evidence for eclipses and we estimate an inclination of 77 deg plus or minus 11 deg. ADS 11060 C is, however, photometrically variable with a period of 9 plus or minus 1 day and an amplitude of 0.05 mag in V. Thus, it is a newly identified BY Draconis variable. The center-of-mass velocity of ADS 11060 C and an estimated parallax of 0.030 sec support its physical association with ADS 11060 AB, making this a quintuple system. The projected separation of the AB-C system is nearly 1200 AU. Although the log lithium abundances of the two components of ADS 11060 C are only upper limits, less than or equal to -0.14, lithium abundances of the AB-C components appear to be consistent with those of similar stars in the alpha Persei and Pleiades clusters, suggesting an age of about 70 Myr for ADS 11060 AB-C. The system is a possible member of the Pleiades moving group. Listed as an optical counterpart to a source in the ROSAT Wide Field Camera extreme-ultraviolet bright source catalog, both ADS 11060 AB and C may contribute to the observed flux.

  9. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia

    PubMed Central

    Saez, Isabel; Duran, Jordi; Sinadinos, Christopher; Beltran, Antoni; Yanes, Oscar; Tevy, María F; Martínez-Pons, Carlos; Milán, Marco; Guinovart, Joan J

    2014-01-01

    Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that—against general belief—neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress. PMID:24569689

  10. NF-Y activates genes of metabolic pathways altered in cancer cells.

    PubMed

    Benatti, Paolo; Chiaramonte, Maria Luisa; Lorenzo, Mariangela; Hartley, John A; Hochhauser, Daniel; Gnesutta, Nerina; Mantovani, Roberto; Imbriano, Carol; Dolfini, Diletta

    2016-01-12

    The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Specific cancer-driving nodes are generally under NF-Y control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production and other anabolic pathways commonly altered in cancer cells.

  11. Effects of fluoride emissions on enzyme activity in metabolism of agricultural plants

    SciTech Connect

    Moeri, P.B.

    1980-01-01

    The effects of fluoride on the activity of malatedehydrogenase (MDH) in rape seed and rye grass have been investigated. Fluoride, which has been absorbed from the air, seems to act differently from fluoride added to the soil. The action of airborne fluoride compounds resorbed by the plant on the activity of MDH significantly correlated with the distance from an aluminum plant, crop yield, and fluoride content. 5 references, 5 figures, 2 tables.

  12. Adding delayed recall to the ADAS-cog improves measurement precision in mild Alzheimer's disease: Implications for predicting instrumental activities of daily living.

    PubMed

    Lowe, Deborah A; Balsis, Steve; Benge, Jared F; Doody, Rachelle S

    2015-12-01

    As research increasingly focuses on preclinical stages of Alzheimer's disease (AD), instruments must be retooled to identify early cognitive markers of AD. A supplemental delayed recall subtest for the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog; Mohs, Rosen, & Davis, 1983; Rosen, Mohs, & Davis, 1984) is commonly implemented, but it is not known precisely where along the spectrum of cognitive dysfunction this subtest yields incremental information beyond what is gained from the standard ADAS-cog, or whether it can improve prediction of functional outcomes. An item response theory approach can analyze this in a psychometrically rigorous way. Seven hundred eighty-eight patients with AD or amnestic complaints or impairment completed a battery including the ADAS-cog and 2 activities of daily living measures. The delayed recall subtest slightly improved the ADAS-cog's measurement precision in the mild range of cognitive dysfunction and increased prediction of instrumental activities of daily living for individuals with subjective memory impairment.

  13. AMBIENT: Active Modules for Bipartite Networks - using high-throughput transcriptomic data to dissect metabolic response

    PubMed Central

    2013-01-01

    Background With the continued proliferation of high-throughput biological experiments, there is a pressing need for tools to integrate the data produced in ways that produce biologically meaningful conclusions. Many microarray studies have analysed transcriptomic data from a pathway perspective, for instance by testing for KEGG pathway enrichment in sets of upregulated genes. However, the increasing availability of species-specific metabolic models provides the opportunity to analyse these data in a more objective, system-wide manner. Results Here we introduce ambient (Active Modules for Bipartite Networks), a simulated annealing approach to the discovery of metabolic subnetworks (modules) that are significantly affected by a given genetic or environmental change. The metabolic modules returned by ambient are connected parts of the bipartite network that change coherently between conditions, providing a more detailed view of metabolic changes than standard approaches based on pathway enrichment. Conclusions ambient is an effective and flexible tool for the analysis of high-throughput data in a metabolic context. The same approach can be applied to any system in which reactions (or metabolites) can be assigned a score based on some biological observation, without the limitation of predefined pathways. A Python implementation of ambient is available at http://www.theosysbio.bio.ic.ac.uk/ambient. PMID:23531303

  14. Genome-scale metabolic modeling to provide insight into the production of storage compounds during feast-famine cycles of activated sludge.

    PubMed

    Tajparast, Mohammad; Frigon, Dominic

    2013-01-01

    Studying storage metabolism during feast-famine cycles of activated sludge treatment systems provides profound insight in terms of both operational issues (e.g., foaming and bulking) and process optimization for the production of value added by-products (e.g., bioplastics). We examined the storage metabolism (including poly-β-hydroxybutyrate [PHB], glycogen, and triacylglycerols [TAGs]) during feast-famine cycles using two genome-scale metabolic models: Rhodococcus jostii RHA1 (iMT1174) and Escherichia coli K-12 (iAF1260) for growth on glucose, acetate, and succinate. The goal was to develop the proper objective function (OF) for the prediction of the main storage compound produced in activated sludge for given feast-famine cycle conditions. For the flux balance analysis, combinations of three OFs were tested. For all of them, the main OF was to maximize growth rates. Two additional sub-OFs were used: (1) minimization of biochemical fluxes, and (2) minimization of metabolic adjustments (MoMA) between the feast and famine periods. All (sub-)OFs predicted identical substrate-storage associations for the feast-famine growth of the above-mentioned metabolic models on a given substrate when glucose and acetate were set as sole carbon sources (i.e., glucose-glycogen and acetate-PHB), in agreement with experimental observations. However, in the case of succinate as substrate, the predictions depended on the network structure of the metabolic models such that the E. coli model predicted glycogen accumulation and the R. jostii model predicted PHB accumulation. While the accumulation of both PHB and glycogen was observed experimentally, PHB showed higher dynamics during an activated sludge feast-famine growth cycle with succinate as substrate. These results suggest that new modeling insights between metabolic predictions and population ecology will be necessary to properly predict metabolisms likely to emerge within the niches of activated sludge communities. Nonetheless

  15. Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

    PubMed Central

    Covarrubias, Anthony J; Aksoylar, Halil Ibrahim; Yu, Jiujiu; Snyder, Nathaniel W; Worth, Andrew J; Iyer, Shankar S; Wang, Jiawei; Ben-Sahra, Issam; Byles, Vanessa; Polynne-Stapornkul, Tiffany; Espinosa, Erika C; Lamming, Dudley; Manning, Brendan D; Zhang, Yijing; Blair, Ian A; Horng, Tiffany

    2016-01-01

    Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation. DOI: http://dx.doi.org/10.7554/eLife.11612.001 PMID:26894960

  16. Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation.

    PubMed

    Covarrubias, Anthony J; Aksoylar, Halil Ibrahim; Yu, Jiujiu; Snyder, Nathaniel W; Worth, Andrew J; Iyer, Shankar S; Wang, Jiawei; Ben-Sahra, Issam; Byles, Vanessa; Polynne-Stapornkul, Tiffany; Espinosa, Erika C; Lamming, Dudley; Manning, Brendan D; Zhang, Yijing; Blair, Ian A; Horng, Tiffany

    2016-02-19

    Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation.

  17. Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation

    PubMed Central

    Hubbard, Troy D.; Murray, Iain A.

    2015-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor recognized for its role in xenobiotic metabolism. The physiologic function of AHR has expanded to include roles in immune regulation, organogenesis, mucosal barrier function, and the cell cycle. These functions are likely dependent upon ligand-mediated activation of the receptor. High-affinity ligands of AHR have been classically defined as xenobiotics, such as polychlorinated biphenyls and dioxins. Identification of endogenous AHR ligands is key to understanding the physiologic functions of this enigmatic receptor. Metabolic pathways targeting the amino acid tryptophan and indole can lead to a myriad of metabolites, some of which are AHR ligands. Many of these ligands exhibit species selective preferential binding to AHR. The discovery of specific tryptophan metabolites as AHR ligands may provide insight concerning where AHR is activated in an organism, such as at the site of inflammation and within the intestinal tract. PMID:26041783

  18. Metabolic alterations induced in cultured skeletal muscle by stretch-relaxation activity

    NASA Technical Reports Server (NTRS)

    Hatfaludy, Sophia; Shansky, Janet; Vandenburgh, Herman H.

    1989-01-01

    Muscle cells differentiated in vitro are repetitively stretched and relaxed in order to determine the presence of short- and long-term alterations occurring in glucose uptake and lactate efflux that are similar to the metabolic alterations occurring in stimulated organ-cultured muscle and in vivo skeletal muscle during the active state. It is observed that whereas mechanical stimulation increases these metabolic parameters within 4-6 h of starting activity, unstimulated basal rates in control cultures also increase during this period of time, and by 8 h, their rates have reached or exceeded the rates in continuously stimulated cells. Measurements of these parameters in media of different compositions show that activity-induced long-term alterations in the parameters occur independently of growth factors in serium and embryo extracts.

  19. In vitro genotoxicity of neutral red after photo-activation and metabolic activation in the Ames test, the micronucleus test and the comet assay.

    PubMed

    Guérard, Melanie; Zeller, Andreas; Singer, Thomas; Gocke, Elmar

    2012-07-04

    Neutral red (Nr) is relatively non-toxic and is widely used as indicator dye in many biological test systems. It absorbs visible light and is known to act as a photosensitizer, involving the generation of reactive oxygen species (type-I reaction) and singlet oxygen (type-II reaction). The mutagenicity of Nr was determined in the Ames test (with Salmonella typhimurium strains TA1535, TA97, TA98, TA98NR, TA100, and TA102) with and without metabolic activation, and with and without photo-activation on agar plates. Similarly to the situation following metabolic activation, photo-mutagenicity of Nr was seen with all Salmonella strains tested, albeit with different effects between these strains. To our knowledge, Nr is the only photo-mutagen showing such a broad action. Since the effects are also observed in strains not known to be responsive to ROS, this indicates that ROS production is not the sole mode of action that leads to photo-genotoxicity. The reactive species produced by irradiation are short-lived as pre-irradiation of an Nr solution did not produce mutagenic effects when added to the bacteria. In addition, mutagenicity in TA98 following irradiation was stronger than in the nitroreductase-deficient strain TA98NR, indicating that nitro derivatives that are transformed by bacterial nitroreductase to hydroxylamines appear to play a role in the photo-mutagenicity of Nr. Photo-genotoxicity of Nr was further investigated in the comet assay and micronucleus test in L5178Y cells. Concentration-dependent increases in primary DNA damage and in the frequency of micronuclei were observed after irradiation.

  20. Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21.

    PubMed

    Cornu, Marion; Oppliger, Wolfgang; Albert, Verena; Robitaille, Aaron M; Trapani, Francesca; Quagliata, Luca; Fuhrer, Tobias; Sauer, Uwe; Terracciano, Luigi; Hall, Michael N

    2014-08-12

    The liver is a key metabolic organ that controls whole-body physiology in response to nutrient availability. Mammalian target of rapamycin (mTOR) is a nutrient-activated kinase and central controller of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1). To investigate the role of hepatic mTOR complex 1 (mTORC1) in whole-body physiology, we generated liver-specific Tsc1 (L-Tsc1 KO) knockout mice. L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Ectopic activation of mTORC1 also caused depletion of hepatic and plasma glutamine, leading to peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-dependent fibroblast growth factor 21 (FGF21) expression in the liver. Injection of glutamine or knockdown of PGC-1α or FGF21 in the liver suppressed the behavioral and metabolic defects due to mTORC1 activation. Thus, mTORC1 in the liver controls whole-body physiology through PGC-1α and FGF21. Finally, mTORC1 signaling correlated with FGF21 expression in human liver tumors, suggesting that treatment of glutamine-addicted cancers with mTOR inhibitors might have beneficial effects at both the tumor and whole-body level.

  1. Metabolic Maintenance of Cell Asymmetry following Division in Activated T Lymphocytes

    PubMed Central

    Verbist, Katherine C.; Guy, Cliff S; Milasta, Sandra; Liedmann, Swantje; Kamiński, Marcin M.; Wang, Ruoning; Green, Douglas R.

    2016-01-01

    Asymmetric cell division (ACD)—the partitioning of cellular components in response to polarizing cues during mitosis—plays roles in differentiation and development1. ACD is important for the self-renewal of neuroblasts in C. elegans and fertilized zygotes in Drosophila, and participates in the development of mammalian nervous and digestive systems1. T lymphocytes, upon activation by antigen-presenting cells (APC), can undergo ACD, wherein the daughter cell proximal to the APC is more likely to differentiate into an effector-like T cell and the distal daughter more likely to differentiate into a memory-like T cell2. Upon activation and prior to cell division, expression of the transcription factor c-Myc drives metabolic reprogramming, necessary for the subsequent proliferative burst3. We found that during the first division of an activated T cell, c-Myc can sort asymmetrically. Asymmetric amino acid transporter distribution, amino acid content, and TORC1 function correlate with c-Myc expression, and both amino acids and TORC1 activity sustain the differences in c-Myc expression in one daughter over the other. Asymmetric c-Myc levels in daughter T cells affect proliferation, metabolism, and differentiation, and these effects are altered by experimental manipulation of TORC1 activity or Myc expression. Therefore, metabolic signaling pathways cooperate with transcription programs to maintain differential cell fates following asymmetric T cell division. PMID:27064903

  2. Chronic social stress in puberty alters appetitive male sexual behavior and neural metabolic activity.

    PubMed

    Bastida, Christel C; Puga, Frank; Gonzalez-Lima, Francisco; Jennings, Kimberly J; Wommack, Joel C; Delville, Yvon

    2014-07-01

    Repeated social subjugation in early puberty lowers testosterone levels. We used hamsters to investigate the effects of social subjugation on male sexual behavior and metabolic activity within neural systems controlling social and motivational behaviors. Subjugated animals were exposed daily to aggressive adult males in early puberty for postnatal days 28 to 42, while control animals were placed in empty clean cages. On postnatal day 45, they were tested for male sexual behavior in the presence of receptive female. Alternatively, they were tested for mate choice after placement at the base of a Y-maze containing a sexually receptive female in one tip of the maze and an ovariectomized one on the other. Social subjugation did not affect the capacity to mate with receptive females. Although control animals were fast to approach females and preferred ovariectomized individuals, subjugated animals stayed away from them and showed no preference. Cytochrome oxidase activity was reduced within the preoptic area and ventral tegmental area in subjugated hamsters. In addition, the correlation of metabolic activity of these areas with the bed nucleus of the stria terminalis and anterior parietal cortex changed significantly from positive in controls to negative in subjugated animals. These data show that at mid-puberty, while male hamsters are capable of mating, their appetitive sexual behavior is not fully mature and this aspect of male sexual behavior is responsive to social subjugation. Furthermore, metabolic activity and coordination of activity in brain areas related to sexual behavior and motivation were altered by social subjugation.

  3. Metabolic equivalents of task are confounded by adiposity, which disturbs objective measurement of physical activity.

    PubMed

    Tompuri, Tuomo T

    2015-01-01

    Physical activity refers any bodily movements produced by skeletal muscles that expends energy. Hence the amount and the intensity of physical activity can be assessed by energy expenditure. Metabolic equivalents of task (MET) are multiplies of the resting metabolism reflecting metabolic rate during exercise. The standard MET is defined as 3.5 ml/min/kg. However, the expression of energy expenditure by body weight to normalize the size differences between subjects causes analytical hazards: scaling by body weight does not have a physiological, mathematical, or physical rationale. This review demonstrates by examples that false methodology may cause paradoxical observations if physical activity would be assessed by body weight scaled values such as standard METs. While standard METs are confounded by adiposity, lean mass proportional measures of energy expenditure would enable a more truthful choice to assess physical activity. While physical activity as a behavior and cardiorespiratory fitness or adiposity as a state represents major determinants of public health, specific measurements of health determinants must be understood to enable a truthful evaluation of the interactions and their independent role as a health predictor.

  4. Effects of High Pressure on Survival and Metabolic Activity of Lactobacillus plantarum TMW1.460

    PubMed Central

    Ulmer, Helge M.; Gänzle, Michael G.; Vogel, Rudi F.

    2000-01-01

    The application of high pressure (HP) for food preservation requires insight into mechanisms of HP-mediated cell injury and death. The HP inactivation in model beer of Lactobacillus plantarum TMW1.460, a beer-spoiling organism, was investigated at pressures ranging from 200 to 600 MPa. Surviving cells were characterized by determination of (i) cell viability and sublethal injury, (ii) membrane permeability to the fluorescent dyes propidium iodide (PI) and ethidium bromide (EB), (iii) metabolic activity with tetrazolium salts, and (iv) the activity of HorA, an ATP binding cassette-type multidrug resistance transporter conferring resistance to hop compounds. HP inactivation curves exhibited a shoulder, an exponential inactivation phase, and pronounced tailing caused by a barotolerant fraction of the population, about 1 in 106 cells. During exponential inactivation, more than 99.99% of cells were sublethally injured; however, no sublethal injury was detected in the barotolerant fraction of the culture. Sublethally injured cells were metabolically active, and loss of metabolic activity corresponded to the decrease of cell viability. Membrane damage measured by PI uptake occurred later than cell death, indicating that dye exclusion may be used as a fail-safe method for preliminary characterization of HP inactivation. An increase of membrane permeability to EB and a reduction of HorA activity were observed prior to the loss of cell viability, indicating loss of hop resistance of pressurized cells. Even mild HP treatments thus abolished the ability of cells to survive under adverse conditions. PMID:10966416

  5. Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21

    PubMed Central

    Cornu, Marion; Oppliger, Wolfgang; Albert, Verena; Robitaille, Aaron M.; Trapani, Francesca; Quagliata, Luca; Fuhrer, Tobias; Sauer, Uwe; Terracciano, Luigi; Hall, Michael N.

    2014-01-01

    The liver is a key metabolic organ that controls whole-body physiology in response to nutrient availability. Mammalian target of rapamycin (mTOR) is a nutrient-activated kinase and central controller of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1). To investigate the role of hepatic mTOR complex 1 (mTORC1) in whole-body physiology, we generated liver-specific Tsc1 (L-Tsc1 KO) knockout mice. L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Ectopic activation of mTORC1 also caused depletion of hepatic and plasma glutamine, leading to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α)–dependent fibroblast growth factor 21 (FGF21) expression in the liver. Injection of glutamine or knockdown of PGC-1α or FGF21 in the liver suppressed the behavioral and metabolic defects due to mTORC1 activation. Thus, mTORC1 in the liver controls whole-body physiology through PGC-1α and FGF21. Finally, mTORC1 signaling correlated with FGF21 expression in human liver tumors, suggesting that treatment of glutamine-addicted cancers with mTOR inhibitors might have beneficial effects at both the tumor and whole-body level. PMID:25082895

  6. Metabolic equivalents of task are confounded by adiposity, which disturbs objective measurement of physical activity

    PubMed Central

    Tompuri, Tuomo T.

    2015-01-01

    Physical activity refers any bodily movements produced by skeletal muscles that expends energy. Hence the amount and the intensity of physical activity can be assessed by energy expenditure. Metabolic equivalents of task (MET) are multiplies of the resting metabolism reflecting metabolic rate during exercise. The standard MET is defined as 3.5 ml/min/kg. However, the expression of energy expenditure by body weight to normalize the size differences between subjects causes analytical hazards: scaling by body weight does not have a physiological, mathematical, or physical rationale. This review demonstrates by examples that false methodology may cause paradoxical observations if physical activity would be assessed by body weight scaled values such as standard METs. While standard METs are confounded by adiposity, lean mass proportional measures of energy expenditure would enable a more truthful choice to assess physical activity. While physical activity as a behavior and cardiorespiratory fitness or adiposity as a state represents major determinants of public health, specific measurements of health determinants must be understood to enable a truthful evaluation of the interactions and their independent role as a health predictor. PMID:26321958

  7. Xenobiotic metabolizing enzyme activities in cells used for testing skin sensitization in vitro.

    PubMed

    Fabian, E; Vogel, D; Blatz, V; Ramirez, T; Kolle, S; Eltze, T; van Ravenzwaay, B; Oesch, F; Landsiedel, R

    2013-09-01

    For ethical and regulatory reasons, in vitro tests for scoring potential toxicities of cosmetics are essential. A test strategy for investigating potential skin sensitization using two human keratinocytic and two human dendritic cell lines has been developed (Mehling et al. Arch Toxicol 86:1273–1295, 2012). Since prohaptens may be metabolically activated in the skin, information on xenobiotic metabolizing enzyme (XME) activities in these cell lines is of high interest. In this study, XME activity assays, monitoring metabolite or cofactor, showed the following: all three passages of keratinocytic (KeratinoSens® and LuSens) and dendritic (U937 und THP-1) cells displayed N-acetyltransferase 1 (NAT1) activities (about 6–60 nmol/min/mg S9-protein for acetylation of para-aminobenzoic acid). This is relevant since reactive species of many cosmetics are metabolically controlled by cutaneous NAT1. Esterase activities of about 1–4 nmol fluorescein diacetate/min/mg S9-protein were observed in all passages of investigated keratinocytic and about 1 nmol fluorescein diacetate/min/mg S9-protein in dendritic cell lines. This is also of practical relevance since many esters and amides are detoxified and others activated by cutaneous esterases. In both keratinocytic cell lines, activities of aldehyde dehydrogenase (ALDH) were observed (5–17 nmol product/min/mg cytosolic protein). ALDH is relevant for the detoxication of reactive aldehydes. Activities of several other XME were below detection, namely the investigated cytochrome P450-dependent alkylresorufin O-dealkylases 7-ethylresorufin O-deethylase, 7-benzylresorufin O-debenzylase and 7-pentylresorufin O-depentylase (while NADPH cytochrome c reductase activities were much above the limit of quantification), the flavin-containing monooxygenase, the alcohol dehydrogenase as well as the UDP glucuronosyl transferase activities.

  8. Physiological community ecology: variation in metabolic activity of ecologically important rocky intertidal invertebrates along environmental gradients.

    PubMed

    Dahlhoff, Elizabeth P; Stillman, Jonathon H; Menge, Bruce A

    2002-08-01

    Rocky intertidal invertebrates live in heterogeneous habitats characterized by steep gradients in wave activity, tidal flux, temperature, food quality and food availability. These environmental factors impact metabolic activity via changes in energy input and stress-induced alteration of energetic demands. For keystone species, small environmentally induced shifts in metabolic activity may lead to disproportionately large impacts on community structure via changes in growth or survival of these key species. Here we use biochemical indicators to assess how natural differences in wave exposure, temperature and food availability may affect metabolic activity of mussels, barnacles, whelks and sea stars living at rocky intertidal sites with different physical and oceanographic characteristics. We show that oxygen consumption rate is correlated with the activity of key metabolic enzymes (e.g., citrate synthase and malate dehydrogenase) for some intertidal species, and concentrations of these enzymes in certain tissues are lower for starved individuals than for those that are well fed. We also show that the ratio of RNA to DNA (an index of protein synthetic capacity) is highly variable in nature and correlates with short-term changes in food availability. We also observed striking patterns in enzyme activity and RNA/DNA in nature, which are related to differences in rocky intertidal community structure. Differences among species and habitats are most pronounced in summer and are linked to high nearshore productivity at sites favored by suspension feeders and to exposure to stressful low-tide air temperatures in areas of low wave splash. These studies illustrate the great promise of using biochemical indicators to test ecological models, which predict changes in community structure along environmental gradients. Our results also suggest that biochemical indices must be carefully validated with laboratory studies, so that the indicator selected is likely to respond to the

  9. [Value-Added--Adding Economic Value in the Food Industry].

    ERIC Educational Resources Information Center

    Welch, Mary A., Ed.

    1989-01-01

    This booklet focuses on the economic concept of "value added" to goods and services. A student activity worksheet illustrates how the steps involved in processing food are examples of the concept of value added. The booklet further links food processing to the idea of value added to the Gross National Product (GNP). Discussion questions,…

  10. Enzyme activities of D-glucose metabolism in the fission yeast Schizosaccharomyces pombe.

    PubMed

    Tsai, C S; Shi, J L; Beehler, B W; Beck, B

    1992-12-01

    The activities of key enzymes that are members of D-glucose metabolic pathways in Schizosaccharomyces pombe undergoing respirative, respirofermentative, and fermentative metabolisms are monitored. The steady-state activities of glycolytic enzymes, except phosphofructokinase, decrease with a reduced efficiency in D-glucose utilization by yeast continuous culture. On the other hand, the enzymic activities of pentose monophosphate pathway reach the maximum when the cell mass production of the cultures is optimum. Enzymes of tricarboxylate cycle exhibit the maximum activities at approximately the washout rate. The steady-state activity of pyruvate dehydrogenase complex increases rapidly when D-glucose is efficiently utilized. By comparison, the activity of pyruvate decarboxylase begins to increase only when ethanol production occurs. Depletion of dissolved oxygen suppresses the activity of pyruvate dehydrogenase complex but facilitates that of pyruvate decarboxylase. Acetate greatly enhances the acetyl CoA synthetase activity. Similarly, ethanol stimulates alcohol dehydrogenase and aldehyde dehydrogenase activities. Evidence for the existence of alcohol dehydrogenase isozymes in the fission yeast is presented.

  11. Metabolic activity and behavior of the invasive amphipod Dikerogammarus villosus and two common Central European gammarid species (Gammarus fossarum, Gammarus roeselii): Low metabolic rates may favor the invader.

    PubMed

    Becker, Jochen; Ortmann, Christian; Wetzel, Markus A; Koop, Jochen H E

    2016-01-01

    The Ponto-Caspian amphipod Dikerogammarus villosus is one of the most successful invaders in Central European rivers. Contrary to studies on its ecology, ecophysiological studies comparing the species' physiological traits are scarce. In this context, in particular the metabolic activity of the invasive species has rarely been considered and, moreover, the few existing studies on this species report strongly deviating results. The purpose of this study was to assess the metabolic activity and behavior of D. villosus and other common European amphipod species (Gammarus fossarum, Gammarus roeselii) in relation to temperatures covering the thermal regime of the invaded habitats. Based on direct calorimetric measurements of metabolic heat dissipation at three temperature levels (5°C, 15°C and 25°C), we found the routine metabolic rate of D. villosus to be significantly lower than that of the other studied gammarid species at the medium temperature level. The estimated resting metabolic rate indicated a similar trend. At 5°C and 25°C, both routine and resting metabolic rate did not differ between species. Compared to G. fossarum and G. roeselii, D. villosus exhibited lower locomotor activity at the low and medium temperatures (5°C and 15°C). In contrast, its locomotor activity increased at the high experimental temperature (25°C). G. fossarum and G. roeselii were apparently more active than D. villosus at all studied temperatures. We conclude that D. villosus has both physiological and behavioral adaptations that lead to a reduction in metabolic energy expenditure, which is assumed to be beneficial and might contribute to its invasive success.

  12. Low resting metabolic rate in exercise-associated amenorrhea is not due to a reduced proportion of highly active metabolic tissue compartments.

    PubMed

    Koehler, Karsten; Williams, Nancy I; Mallinson, Rebecca J; Southmayd, Emily A; Allaway, Heather C M; De Souza, Mary Jane

    2016-08-01

    Exercising women with menstrual disturbances frequently display a low resting metabolic rate (RMR) when RMR is expressed relative to body size or lean mass. However, normalizing RMR for body size or lean mass does not account for potential differences in the size of tissue compartments with varying metabolic activities. To explore whether the apparent RMR suppression in women with exercise-associated amenorrhea is a consequence of a lower proportion of highly active metabolic tissue compartments or the result of metabolic adaptations related to energy conservation at the tissue level, RMR and metabolic tissue compartments were compared among exercising women with amenorrhea (AMEN; n = 42) and exercising women with eumenorrheic, ovulatory menstrual cycles (OV; n = 37). RMR was measured using indirect calorimetry and predicted from the size of metabolic tissue compartments as measured by dual-energy X-ray absorptiometry (DEXA). Measured RMR was lower than DEXA-predicted RMR in AMEN (1,215 ± 31 vs. 1,327 ± 18 kcal/day, P < 0.001) but not in OV (1,284 ± 24 vs. 1,252 ± 17, P = 0.16), resulting in a lower ratio of measured to DEXA-predicted RMR in AMEN (91 ± 2%) vs. OV (103 ± 2%, P < 0.001). AMEN displayed proportionally more residual mass (P < 0.001) and less adipose tissue (P = 0.003) compared with OV. A lower ratio of measured to DXA-predicted RMR was associated with lower serum total triiodothyronine (ρ = 0.38, P < 0.001) and leptin (ρ = 0.32, P = 0.004). Our findings suggest that RMR suppression in this population is not the result of a reduced size of highly active metabolic tissue compartments but is due to metabolic and endocrine adaptations at the tissue level that are indicative of energy conservation.

  13. Orbital fluid shear stress promotes osteoblast metabolism, proliferation and alkaline phosphates activity in vitro.

    PubMed

    Aisha, M D; Nor-Ashikin, M N K; Sharaniza, A B R; Nawawi, H; Froemming, G R A

    2015-09-10

    Prolonged disuse of the musculoskeletal system is associated with reduced mechanical loading and lack of anabolic stimulus. As a form of mechanical signal, the multidirectional orbital fluid shear stress transmits anabolic signal to bone forming cells in promoting cell differentiation, metabolism and proliferation. Signals are channeled through the cytoskeleton framework, directly modifying gene and protein expression. For that reason, we aimed to study the organization of Normal Human Osteoblast (NHOst) cytoskeleton with regards to orbital fluid shear (OFS) stress. Of special interest were the consequences of cytoskeletal reorganization on NHOst metabolism, proliferation, and osteogenic functional markers. Cells stimulated at 250 RPM in a shaking incubator resulted in the rearrangement of actin and tubulin fibers after 72 h. Orbital shear stress increased NHOst mitochondrial metabolism and proliferation, simultaneously preventing apoptosis. The ratio of RANKL/OPG was reduced, suggesting that orbital shear stress has the potential to inhibit osteoclastogenesis and osteoclast activity. Increase in ALP activity and OCN protein production suggests that stimulation retained osteoblast function. Shear stress possibly generated through actin seemed to hold an anabolic response as osteoblast metabolism and functional markers were enhanced. We hypothesize that by applying orbital shear stress with suitable magnitude and duration as a non-drug anabolic treatment can help improve bone regeneration in prolonged disuse cases.

  14. Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses.

    PubMed

    Ou, Yang; Wang, Shang-Jui; Li, Dawei; Chu, Bo; Gu, Wei

    2016-11-01

    Although p53-mediated cell-cycle arrest, senescence, and apoptosis remain critical barriers to cancer development, the emerging role of p53 in cell metabolism, oxidative responses, and ferroptotic cell death has been a topic of great interest. Nevertheless, it is unclear how p53 orchestrates its activities in multiple metabolic pathways into tumor suppressive effects. Here, we identified the SAT1 (spermidine/spermine N(1)-acetyltransferase 1) gene as a transcription target of p53. SAT1 is a rate-limiting enzyme in polyamine catabolism critically involved in the conversion of spermidine and spermine back to putrescine. Surprisingly, we found that activation of SAT1 expression induces lipid peroxidation and sensitizes cells to undergo ferroptosis upon reactive oxygen species (ROS)-induced stress, which also leads to suppression of tumor growth in xenograft tumor models. Notably, SAT1 expression is down-regulated in human tumors, and CRISPR-cas9-mediated knockout of SAT1 expression partially abrogates p53-mediated ferroptosis. Moreover, SAT1 induction is correlated with the expression levels of arachidonate 15-lipoxygenase (ALOX15), and SAT1-induced ferroptosis is significantly abrogated in the presence of PD146176, a specific inhibitor of ALOX15. Thus, our findings uncover a metabolic target of p53 involved in ferroptotic cell death and provide insight into the regulation of polyamine metabolism and ferroptosis-mediated tumor suppression.

  15. Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet.

    PubMed

    Pu, Peng; Gao, Dong-Mei; Mohamed, Salim; Chen, Jing; Zhang, Jing; Zhou, Xiao-Ya; Zhou, Nai-Jing; Xie, Jing; Jiang, Hong

    2012-02-01

    Metabolic syndrome is a low-grade inflammatory state in which oxidative stress is involved. Naringin, isolated from the Citrussinensis, is a phenolic compound with anti-oxidative and anti-inflammatory activities. The aim of this study was to explore the effects of naringin on metabolic syndrome in mice. The animal models, induced by high-fat diet in C57BL/6 mice, developed obesity, dyslipidemia, fatty liver, liver dysfunction and insulin resistance. These changes were attenuated by naringin. Further investigations revealed that the inhibitory effect on inflammation and insulin resistance was mediated by blocking activation of the MAPKs pathways and by activating IRS1; the lipid-lowering effect was attributed to inhibiting the synthesis way and increasing fatty acid oxidation; the hypoglycemic effect was due to the regulation of PEPCK and G6pase. The anti-oxidative stress of naringin also participated in the improvement of insulin resistance and lipogenesis. All of these depended on the AMPK activation. To confirm the results of the animal experiment, we tested primary hepatocytes exposed to high glucose system. Naringin was protective by phosphorylating AMPKα and IRS1. Taken together, these results suggested that naringin protected mice exposed to a high-fat diet from metabolic syndrome through an AMPK-dependent mechanism involving multiple types of intracellular signaling and reduction of oxidative damage.

  16. Inhibition of all-TRANS-retinoic acid metabolism by R116010 induces antitumour activity

    PubMed Central

    Van heusden, J; Van Ginckel, R; Bruwiere, H; Moelans, P; Janssen, B; Floren, W; van der Leede, B J; van Dun, J; Sanz, G; Venet, M; Dillen, L; Van Hove, C; Willemsens, G; Janicot, M; Wouters, W

    2002-01-01

    All-trans-retinoic acid is a potent inhibitor of cell proliferation and inducer of differentiation. However, the clinical use of all-trans-retinoic acid in the treatment of cancer is significantly hampered by its toxicity and the prompt emergence of resistance, believed to be caused by increased all-trans-retinoic acid metabolism. Inhibitors of all-trans-retinoic acid metabolism may therefore prove valuable in the treatment of cancer. In this study, we characterize R116010 as a new anticancer drug that is a potent inhibitor of all-trans-retinoic acid metabolism. In vitro, R116010 potently inhibits all-trans-retinoic acid metabolism in intact T47D cells with an IC50-value of 8.7 nM. In addition, R116010 is a selective inhibitor as indicated by its inhibition profile for several other cytochrome P450-mediated reactions. In T47D cell proliferation assays, R116010 by itself has no effect on cell proliferation. However, in combination with all-trans-retinoic acid, R116010 enhances the all-trans-retinoic acid-mediated antiproliferative activity in a concentration-dependent manner. In vivo, the growth of murine oestrogen-independent TA3-Ha mammary tumours is significantly inhibited by R116010 at doses as low as 0.16 mg kg−1. In conclusion, R116010 is a highly potent and selective inhibitor of all-trans-retinoic acid metabolism, which is able to enhance the biological activity of all-trans-retinoic acid, thereby exhibiting antitumour activity. R116010 represents a novel and promising anticancer drug with an unique mechanism of action. British Journal of Cancer (2002) 86, 605–611. DOI: 10.1038/sj/bjc/6600056 www.bjcancer.com © 2002 Cancer Research UK PMID:11870544

  17. Inhibition of all-TRANS-retinoic acid metabolism by R116010 induces antitumour activity.

    PubMed

    Van Heusden, J; Van Ginckel, R; Bruwiere, H; Moelans, P; Janssen, B; Floren, W; van der Leede, B J; van Dun, J; Sanz, G; Venet, M; Dillen, L; Van Hove, C; Willemsens, G; Janicot, M; Wouters, W

    2002-02-12

    All-trans-retinoic acid is a potent inhibitor of cell proliferation and inducer of differentiation. However, the clinical use of all-trans-retinoic acid in the treatment of cancer is significantly hampered by its toxicity and the prompt emergence of resistance, believed to be caused by increased all-trans-retinoic acid metabolism. Inhibitors of all-trans-retinoic acid metabolism may therefore prove valuable in the treatment of cancer. In this study, we characterize R116010 as a new anticancer drug that is a potent inhibitor of all-trans-retinoic acid metabolism. In vitro, R116010 potently inhibits all-trans-retinoic acid metabolism in intact T47D cells with an IC(50)-value of 8.7 nM. In addition, R116010 is a selective inhibitor as indicated by its inhibition profile for several other cytochrome P450-mediated reactions. In T47D cell proliferation assays, R116010 by itself has no effect on cell proliferation. However, in combination with all-trans-retinoic acid, R116010 enhances the all-trans-retinoic acid-mediated antiproliferative activity in a concentration-dependent manner. In vivo, the growth of murine oestrogen-independent TA3-Ha mammary tumours is significantly inhibited by R116010 at doses as low as 0.16 mg kg(-1). In conclusion, R116010 is a highly potent and selective inhibitor of all-trans-retinoic acid metabolism, which is able to enhance the biological activity of all-trans-retinoic acid, thereby exhibiting antitumour activity. R116010 represents a novel and promising anticancer drug with an unique mechanism of action.

  18. Seasonal variation in metabolic rate, flight activity and body size of Anopheles gambiae in the Sahel

    PubMed Central

    Huestis, Diana L.; Yaro, Alpha S.; Traoré, Adama I.; Dieter, Kathryne L.; Nwagbara, Juliette I.; Bowie, Aleah C.; Adamou, Abdoulaye; Kassogué, Yaya; Diallo, Moussa; Timbiné, Seydou; Dao, Adama; Lehmann, Tovi

    2012-01-01

    SUMMARY Malaria in Africa is vectored primarily by the Anopheles gambiae complex. Although the mechanisms of population persistence during the dry season are not yet known, targeting dry season mosquitoes could provide opportunities for vector control. In the Sahel, it appears likely that M-form A. gambiae survive by aestivation (entering a dormant state). To assess the role of eco-physiological changes associated with dry season survival, we measured body size, flight activity and metabolic rate of wild-caught mosquitoes throughout 1 year in a Sahelian locality, far from permanent water sources, and at a riparian location adjacent to the Niger River. We found significant seasonal variation in body size at both the Sahelian and riparian sites, although the magnitude of the variation was greater in the Sahel. For flight activity, significant seasonality was only observed in the Sahel, with increased flight activity in the wet season when compared with that just prior to and throughout the dry season. Whole-organism metabolic rate was affected by numerous biotic and abiotic factors, and a significant seasonal component was found at both locations. However, assay temperature accounted completely for seasonality at the riparian location, while significant seasonal variation remained after accounting for all measured variables in the Sahel. Interestingly, we did not find that mean metabolic rate was lowest during the dry season at either location, contrary to our expectation that mosquitoes would conserve energy and increase longevity by reducing metabolism during this time. These results indicate that mosquitoes may use mechanisms besides reduced metabolic rate to enable survival during the Sahelian dry season. PMID:22623189

  19. Magnesium deficiency and metabolic syndrome: stress and inflammation may reflect calcium activation.

    PubMed

    Rayssiguier, Yves; Libako, Patrycja; Nowacki, Wojciech; Rock, Edmond

    2010-06-01

    Magnesium (Mg) intake is inadequate in the western diet and metabolic syndrome is highly prevalent in populations around the world. Epidemiological studies suggest that high Mg intake may reduce the risk but the possibility of confounding factors exists, given the strong association between Mg and other beneficial nutriments (vegetables, fibers, cereals). The concept that metabolic syndrome is an inflammatory condition may explain the role of Mg.Mg deficiency results in a stress effect and increased susceptibility to physiological damage produced by stress. Stress activates the hypothalamic-pituitary-adrenal axis (HPA) axis and the sympathetic nervous system. The activation of the renin-angiotensin-aldosterone system is a factor in the development of insulin resistance by increasing oxidative stress. In both humans and rats, aldosteronism results in an immunostimulatory state and leads to an inflammatory phenotype. Stress response induces the release of large quantities of excitatory amino acids and activates the nuclear factor NFkappaB, promoting translation of molecules involved in cell regulation, metabolism and apoptosis. The rise in neuropeptides is also well documented. Stress-induced HPA activation has been identified to play an important role in the preferential body fat accumulation but evidence that Mg is involved in body weight regulation is lacking. One of the earliest events in the acute response to stress is endothelial dysfunction. Endothelial cells actively contribute to inflammation by elaborating cytokines, synthesizing chemical mediators and expressing adhesion molecules. Experimental Mg deficiency in rats induces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, synthesis of inflammatory cytokines and acute phase proteins, extensive production of free radicals. An increase in extracellular Mg concentration decreases inflammatory effects, while reduction in extracellular Mg results in cell activation. The

  20. Human Aldo-Keto Reductases and the Metabolic Activation of Polycyclic Aromatic Hydrocarbons

    PubMed Central

    2015-01-01

    Aldo-keto reductases (AKRs) are promiscuous NAD(P)(H) dependent oxidoreductases implicated in the metabolic activation of polycyclic aromatic hydrocarbons (PAH). These enzymes catalyze the oxidation of non-K-region trans-dihydrodiols to the corresponding o-quinones with the concomitant production of reactive oxygen species (ROS). The PAH o-quinones are Michael acceptors and can form adducts but are also redox-active and enter into futile redox cycles to amplify ROS formation. Evidence exists to support this metabolic pathway in humans. The human recombinant AKR1A1 and AKR1C1–AKR1C4 enzymes all catalyze the oxidation of PAH trans-dihydrodiols to PAH o-quinones. Many human AKRs also catalyze the NADPH-dependent reduction of the o-quinone products to air-sensitive catechols, exacerbating ROS formation. Moreover, this pathway of PAH activation occurs in a panel of human lung cell lines, resulting in the production of ROS and oxidative DNA damage in the form of 8-oxo-2′-deoxyguanosine. Using stable-isotope dilution liquid chromatography tandem mass spectrometry, this pathway of benzo[a]pyrene (B[a]P) metabolism was found to contribute equally with the diol-epoxide pathway to the activation of this human carcinogen in human lung cells. Evaluation of the mutagenicity of anti-B[a]P-diol epoxide with B[a]P-7,8-dione on p53 showed that the o-quinone produced by AKRs was the more potent mutagen, provided that it was permitted to redox cycle, and that the mutations observed were G to T transversions, reminiscent of those observed in human lung cancer. It is concluded that there is sufficient evidence to support the role of human AKRs in the metabolic activation of PAH in human lung cell lines and that they may contribute to the causation of human lung cancer. PMID:25279998

  1. Motility, ATP levels and metabolic enzyme activity of sperm from bluegill (Lepomis macrochirus).

    PubMed

    Burness, Gary; Moyes, Christopher D; Montgomerie, Robert

    2005-01-01

    Male bluegill displays one of two life history tactics. Some males (termed "parentals") delay reproduction until ca. 7 years of age, at which time they build nests and actively courts females. Others mature precociously (sneakers) and obtain fertilizations by cuckolding parental males. In the current study, we studied the relations among sperm motility, ATP levels, and metabolic enzyme activity in parental and sneaker bluegill. In both reproductive tactics, sperm swimming speed and ATP levels declined in parallel over the first 60 s of motility. Although sneaker sperm initially had higher ATP levels than parental sperm, by approximately 30 s postactivation, no differences existed between tactics. No differences were noted between tactics in swimming speed, percent motility, or the activities of key metabolic enzymes, although sperm from parentals had a higher ratio of creatine phosphokinase (CPK) to citrate synthase (CS). In both tactics, with increasing CPK and CS activity, sperm ATP levels increased at 20 s postactivation, suggesting that capacities for phosphocreatine hydrolysis and aerobic metabolism may influence interindividual variation in rates of ATP depletion. Nonetheless, there was no relation between sperm ATP levels and either swimming speed or percent of sperm that were motile. This suggests that interindividual variation in ATP levels may not be the primary determinant of variation in sperm swimming performance in bluegill.

  2. Body metabolic rate and electromyographic activities of antigravitational muscles in supine and standing postures.

    PubMed

    Rubini, Alessandro; Paoli, Antonio; Parmagnani, Andrea

    2012-06-01

    We measured metabolic (oxygen uptake, carbon dioxide production, respiratory ratio), cardio-circulatory (heart rate, systolic and diastolic arterial blood pressure, rate-pressure product, an index of myocardial oxygen consumption calculated by multiplying heart rate by systolic pressure) and electromyographic (integrated electromyographic activities of two antigravitational muscles of the lower limb, soleus and gastrocnemius) variables on 12 young healthy subjects in supine and standing positions at rest. We found statistically significant increments of oxygen uptake, carbon dioxide production, heart rate and integrated electromyographic activities in standing versus supine position. Rate-pressure product increased but not significantly, and no other significant changes were detected. We conclude that postural changes influence metabolic rate, antigravitational muscle reflex activities, and heart rate. A significant positive correlation was found between oxygen uptake and carbon dioxide production and integrated electromyographic activities of antigravitational muscles, while the same was not found for cardio-circulatory variables. These results suggest that the increased metabolic rate in standing position is, at least in part, due to antigravitational muscle tone.

  3. Relationship between physical activity, physical fitness and multiple metabolic risk in youths from Muzambinho's study.

    PubMed

    Barbosa, João Paulo Dos Anjos Souza; Basso, Luciano; Seabra, André; Prista, Antonio; Tani, Go; Maia, José António Ribeiro; Forjaz, Cláudia Lúcia De Moraes

    2016-08-01

    Negative associations between physical activity (PA), physical fitness and multiple metabolic risk factors (MMRF) in youths from populations with low PA are reported. The persistence of this association in moderately-to highly active populations is not, however, well established. The aim of the present study was to investigate this association in a Brazilian city with high frequency of active youths. We assessed 122 subjects (9.9 ± 1.3 years) from Muzambinho city. Body mass index, waist circumference, glycaemia, cholesterolaemia, systolic and diastolic blood pressures were measured. Maximal handgrip strength and one-mile walk/run test were used. Leisure time PA was assessed by interview. Poisson regression was used in the analysis. The model explained 11% of the total variance. Only relative muscular strength and one-mile walk/run were statistically significant (p < .05). Those who needed more time to cover the one-mile walk/run test had an increased in metabolic risk of 11%, and those with greater strength reduced the risk by about 82%. In conclusion, children and youths from an active population who need less time to cover the one-mile walk/run test or who had greater muscular strength showed a reduced metabolic risk. These results suggest that even in children and youths with high leisure time PA, a greater aerobic fitness and strength might help to further reduce their MMRF.

  4. Antiandrogenic activity and metabolism of the organophosphorus pesticide fenthion and related compounds.

    PubMed Central

    Kitamura, Shigeyuki; Suzuki, Tomoharu; Ohta, Shigeru; Fujimoto, Nariaki

    2003-01-01

    We investigated the endocrine-disrupting actions of the organophosphorus pesticide fenthion and related compounds and the influence of metabolic transformation on the activities of these compounds. Fenthion acted as an antagonist of the androgenic activity of dihydrotestosterone (10(-7)M) in the concentration range of 10(-6)-10(-4)M in an androgen-responsive element-luciferase reporter-responsive assay using NIH3T3 cells. The antiandrogenic activity of fenthion was similar in magnitude to that of flutamide. Fenthion also tested positive in the Hershberger assay using castrated male rats. Marked estrogenic and antiestrogenic activities of fenthion and related compounds were not observed in MCF-7 cells. When fenthion was incubated with rat liver microsomes in the presence of NADPH, the antiandrogenic activity markedly decreased, and fenthion sulfoxide was detected as a major metabolite. The oxidase activity toward fenthion was exhibited by cytochrome P450 and flavin-containing monooxygenase. Fenthion sulfoxide was negative in the screening test for antiandrogens, as was fenthion sulfone. However, when fenthion sulfoxide was incubated with liver cytosol in the presence of 2-hydroxypyrimidine, an electron donor of aldehyde oxidase, the extract of the incubation mixture exhibited antiandrogenic activity. In this case, fenthion was detected as a major metabolite of the sulfoxide. Metabolic interconversion between fenthion and fenthion sulfoxide in the body seems to maintain the antiandrogenic activity. PMID:12676606

  5. The contrasting effects of ad libitum and restricted feeding of a diet very high in saturated fats on sex ratio and metabolic hormones in mice.

    PubMed

    Alexenko, Andrei P; Mao, Jiude; Ellersieck, Mark R; Davis, Angela M; Whyte, Jeffrey J; Rosenfeld, Cheryl S; Roberts, R Michael

    2007-10-01

    Skewing of the sex ratio towards males occurs among pups born to mice fed a very high saturated fat (VHF) diet. In the present study, we tested whether the fat content of the VHF diet rather than the number of calories consumed is responsible for this effect. Eight-week-old NIH Swiss mice were placed on the VHF diet either ad libitum (VHF) or in a restricted manner (VHF-R). The VHF-R mice gained weight at a similar rate to controls fed a standard chow diet. Mice were bred at 15 wk and subsequently at 26 wk and 35 wk of age. Overall, the VHF, VHF-R, and control groups delivered 244, 242, and 274 pups, respectively, with male proportions of 0.60, 0.43, and 0.48, respectively. The pup sex ratios of the VHF group (favoring males) and VHF-R group (favoring females) each differed from 0.5 (P < 0.01). The sex ratios also differed (P < 0.0001) between the VHF and control groups, and between the VHF and VHF-R groups. Within the diet groups, maternal body weight had no effect on sex ratio. Serum leptin concentrations among the dams were similar in the VHF and VHF-R groups but higher than in the control group, while the IGF1 and corticosterone levels were comparable in all three groups. Therefore, the atypical sex ratios of offspring born to dams on the VHF diet seem to be influenced by the amount of fat consumed. Since males fed the VHF diet had neither more Y-sperm nor sired more sons than daughters, the dietary effects are manifested exclusively through the female.

  6. Effects of Feeding Milk Replacer Ad Libitum or in Restricted Amounts for the First Five Weeks of Life on the Growth, Metabolic Adaptation, and Immune Status of Newborn Calves

    PubMed Central

    Schäff, Christine T.; Gruse, Jeannine; Maciej, Josefine; Mielenz, Manfred; Wirthgen, Elisa; Hoeflich, Andreas; Schmicke, Marion; Pfuhl, Ralf; Jawor, Paulina; Stefaniak, Tadeusz

    2016-01-01

    The pre-weaning period is critical for calf health and growth, and intensive milk feeding programs may assist postnatal development by improving body growth and organ maturation. The aim of the present work was to study the effects of ad libitum milk replacer (MR) feeding on the growth, metabolic adaptation, health, and immune status of newborn calves. Twenty-eight newborn Holstein and Holstein x Charolais crossbred calves were fed ad libitum (ADLIB) or in restricted amounts (6 liters per day; RES) during the first five weeks of life. The MR intake in the ADLIB treatment was gradually reduced at weeks 6 and 7, and all calves then received 6 liters of MR per day until day 60. Blood samples were collected to measure the plasma concentrations of metabolites, insulin, insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBP), immunoglobulins, and acute phase proteins. The expression of mRNA associated with both the somatotropic axis and gluconeogenic enzymes was measured in the liver on day 60. Intensive feeding improved MR intake and growth in ADLIB without influencing concentrate intake. Carcass weight, perirenal fat, and muscle mass were greater in ADLIB. Plasma concentrations of glucose, triglycerides, insulin, and IGF-I were greater, whereas plasma concentrations of β-hydroxybutyrate, total protein, albumin, urea, IGFBP-2 and -4, and fibrinogen were lower at distinct time points in ADLIB. The hepatic mRNA expression of cytosolic phosphoenolpyruvate carboxykinase was greater in ADLIB. Most metabolic and endocrine differences occurred during the MR feeding period, but a slightly greater concentrate intake was associated with increased plasma IGF-I and insulin at the end of the study. The immune and health status of the calves were not affected by MR feeding. However, increased plasma fibrinogen in the RES group suggested differences in the acute phase response. PMID:28036351

  7. [Detection of viable metabolically active yeast cells using a colorimetric assay].

    PubMed

    Růzicka, F; Holá, V

    2008-02-01

    The increasing concern of yeasts able to form biofilm brings about the need for susceptibility testing of both planktonic and biofilm cells. Detection of viability or metabolic activity of yeast cells after exposure to antimicrobials plays a key role in the assessment of susceptibility testing results. Colorimetric assays based on the color change of the medium in the presence of metabolically active cells proved suitable for this purpose. In this study, the usability of a colorimetric assay with the resazurin redox indicator for monitoring the effect of yeast inoculum density on the reduction rate was tested. As correlation between the color change rate and inoculum density was observed, approximate quantification of viable cells was possible. The assay would be of relevance to antifungal susceptibility testing in both planktonic and biofilm yeasts.

  8. Stress and host immunity amplify Mycobacterium tuberculosis phenotypic heterogeneity and induce nongrowing metabolically active forms.

    PubMed

    Manina, Giulia; Dhar, Neeraj; McKinney, John D

    2015-01-14

    Nonreplicating and metabolically quiescent bacteria are implicated in latent tuberculosis infections and relapses following "sterilizing" chemotherapy. However, evidence linking bacterial dormancy and persistence in vivo is largely inconclusive. Here we measure the single-cell dynamics of Mycobacterium tuberculosis replication and ribosomal activity using quantitative time-lapse microscopy and a reporter of ribosomal RNA gene expression. Single-cell dynamics exhibit heterogeneity under standard growth conditions, which is amplified by stressful conditions such as nutrient limitation, stationary phase, intracellular replication, and growth in mouse lungs. Additionally, the lungs of chronically infected mice harbor a subpopulation of nongrowing but metabolically active bacteria, which are absent in mice lacking interferon-γ, a cytokine essential for antituberculosis immunity. These cryptic bacterial forms are prominent in mice treated with the antituberculosis drug isoniazid, suggesting a role in postchemotherapeutic relapses. Thus, amplification of bacterial phenotypic heterogeneity in response to host immunity and drug pressure may contribute to tuberculosis persistence.

  9. Orbital fluid shear stress promotes osteoblast metabolism, proliferation and alkaline phosphates activity in vitro

    SciTech Connect

    Aisha, M.D.; Nor-Ashikin, M.N.K.; Sharaniza, A.B.R.; Nawawi, H.; Froemming, G.R.A.

    2015-09-10

    Prolonged disuse of the musculoskeletal system is associated with reduced mechanical loading and lack of anabolic stimulus. As a form of mechanical signal, the multidirectional orbital fluid shear stress transmits anabolic signal to bone forming cells in promoting cell differentiation, metabolism and proliferation. Signals are channeled through the cytoskeleton framework, directly modifying gene and protein expression. For that reason, we aimed to study the organization of Normal Human Osteoblast (NHOst) cytoskeleton with regards to orbital fluid shear (OFS) stress. Of special interest were the consequences of cytoskeletal reorganization on NHOst metabolism, proliferation, and osteogenic functional markers. Cells stimulated at 250 RPM in a shaking incubator resulted in the rearrangement of actin and tubulin fibers after 72 h. Orbital shear stress increased NHOst mitochondrial metabolism and proliferation, simultaneously preventing apoptosis. The ratio of RANKL/OPG was reduced, suggesting that orbital shear stress has the potential to inhibit osteoclastogenesis and osteoclast activity. Increase in ALP activity and OCN protein production suggests that stimulation retained osteoblast function. Shear stress possibly generated through actin seemed to hold an anabolic response as osteoblast metabolism and functional markers were enhanced. We hypothesize that by applying orbital shear stress with suitable magnitude and duration as a non-drug anabolic treatment can help improve bone regeneration in prolonged disuse cases. - Highlights: • OFS stress transmits anabolic signals to osteoblasts. • Actin and tubulin fibers are rearranged under OFS stress. • OFS stress increases mitochondrial metabolism and proliferation. • Reduced RANKL/OPG ratio in response to OFS inhibits osteoclastogenesis. • OFS stress prevents apoptosis and stimulates ALP and OCN.

  10. Effect of Metabolic Stress on Coenzyme Q10 Content in Tissues of Active and Passive Rats.

    PubMed

    Kirbaeva, N V; Sharanova, N E; Baturina, V A; Zhminchenko, V M; Pertsov, S S; Vasil'ev, A V

    2016-09-01

    The dynamics of coenzyme Q10 concentration in the blood plasma, liver, and brain of passive and active rats was studied on the model of metabolic stress. This parameter was shown to differ in rats with various patterns of behavior. Dietary consumption of coenzyme Q10 in doses of 10 and 100 mg/kg body weight was followed by changes in its content in experimental animals.

  11. Preparation of Metabolically Active Staphylococcus aureus Protoplasts by Use of the Aeromonas hydrophila Lytic Enzyme

    PubMed Central

    Coles, N. W.; Gross, R.

    1973-01-01

    Stable, metabolically active protoplasts of Staphylococcus aureus have been prepared by the use of a staphylolytic enzyme produced by Aeromonas hydrophila. Respiratory and glycolytic rates and synthesis of nucleic acids, protein, and lipid in these protoplasts, stabilized variously in 1.1 M sucrose, 0.37 M sodium succinate, or 0.37 M sodium sulfate, have been shown to be comparable with the same parameters in intact cells under the same conditions. Images PMID:4728270

  12. [Interaction between CYP450 enzymes and metabolism of traditional Chinese medicine as well as enzyme activity assay].

    PubMed

    Lu, Tu-lin; Su, Lian-lin; Ji, De; Gu, Wei; Mao, Chun-qin

    2015-09-01

    Drugs are exogenous compounds for human bodies, and will be metabolized by many enzymes after administration. CYP450 enzyme, as a major metabolic enzyme, is an important phase I drug metabolizing enzyme. In human bodies, about 75% of drug metabolism is conducted by CYP450 enzymes, and CYP450 enzymes is the key factor for drug interactions between traditional Chinese medicine( TCM) -TCM, TCM-medicine and other drug combination. In order to make clear the interaction between metabolic enzymes and TCM metabolism, we generally chose the enzymatic activity as an evaluation index. That is to say, the enhancement or reduction of CYP450 enzyme activity was used to infer the inducing or inhibitory effect of active ingredients and extracts of traditional Chinese medicine on enzymes. At present, the common method for measuring metabolic enzyme activity is Cocktail probe drugs, and it is the key to select the suitable probe substrates. This is of great significance for study drug's absorption, distribution, metabolism and excretion (ADME) process in organisms. The study focuses on the interaction between TCMs, active ingredients, herbal extracts, cocktail probe substrates as well as CYP450 enzymes, in order to guide future studies.

  13. Physical Activity and Sedentary Behavior in Metabolically Healthy versus Unhealthy Obese and Non-Obese Individuals – The Maastricht Study

    PubMed Central

    van der Berg, Julianne D.; van der Kallen, Carla J. H.; Schram, Miranda T.; Savelberg, Hans H. C. M.; Schaper, Nicolaas C.; Dagnelie, Pieter C.; Henry, Ronald M. A.; Kroon, Abraham A.; Stehouwer, Coen D. A.; Koster, Annemarie

    2016-01-01

    Background Both obesity and the metabolic syndrome are associated with increased risk of cardiovascular diseases and type 2 diabetes. Although both frequently occur together in the same individual, obesity and the metabolic syndrome can also develop independently from each other. The (patho)physiology of “metabolically healthy obese” (i.e. obese without metabolic syndrome) and “metabolically unhealthy non-obese” phenotypes (i.e. non-obese with metabolic syndrome) is not fully understood, but physical activity and sedentary behavior may play a role. Objective To examine objectively measured physical activity and sedentary behavior across four groups: I) “metabolically healthy obese” (MHO); II) “metabolically unhealthy obese” (MUO); III)”metabolically healthy non-obese” (MHNO); and IV) “metabolically unhealthy non-obese” (MUNO). Methods Data were available from 2,449 men and women aged 40–75 years who participated in The Maastricht Study from 2010 to 2013. Participants were classified into the four groups according to obesity (BMI≥30kg/m2) and metabolic syndrome (ATPIII definition). Daily activity was measured for 7 days with the activPAL physical activity monitor and classified as time spent sitting, standing, and stepping. Results In our study population, 562 individuals were obese. 19.4% of the obese individuals and 72.7% of the non-obese individuals was metabolically healthy. After adjustments for age, sex, educational level, smoking, alcohol use, waking time, T2DM, history of CVD and mobility limitation, MHO (n = 107) spent, per day, more time stepping (118.2 versus 105.2 min; p<0.01) and less time sedentary (563.5 versus 593.0 min., p = 0.02) than MUO (n = 440). In parallel, MHNO (n = 1384) spent more time stepping (125.0 versus 115.4 min; p<0.01) and less time sedentary (553.3 versus 576.6 min., p<0.01) than MUNO (n = 518). Conclusion Overall, the metabolically healthy groups were less sedentary and more physically active than the

  14. Metabolic Activity and Functional Diversity Changes in Sediment Prokaryotic Communities Organically Enriched with Mussel Biodeposits

    PubMed Central

    Pollet, Thomas; Cloutier, Olivier; Nozais, Christian; McKindsey, Christopher W.; Archambault, Philippe

    2015-01-01

    This experimental microcosm study reports the influence of organic enrichments by mussel biodeposits on the metabolic activity and functional diversity of benthic prokaryotic communities. The different biodeposit enrichment regimes created, which mimicked the quantity of faeces and pseudo-faeces potentially deposited below mussel farms, show a clear stimulatory effect of this organic enrichment on prokaryotic metabolic activity. This effect was detected once a certain level of biodeposition was attained with a tipping point estimated between 3.25 and 10 g day-1 m-2. Prokaryotic communities recovered their initial metabolic activity by 11 days after the cessation of biodeposit additions. However, their functional diversity remained greater than prior to the disturbance suggesting that mussel biodeposit enrichment may disturb the functioning and perhaps the role of prokaryotic communities in benthic ecosystems. This manipulative approach provided new information on the influence of mussel biodeposition on benthic prokaryotic communities and dose-response relationships and may support the development of carrying capacity models for bivalve culture. PMID:25923715

  15. Metabolic activity and functional diversity changes in sediment prokaryotic communities organically enriched with mussel biodeposits.

    PubMed

    Pollet, Thomas; Cloutier, Olivier; Nozais, Christian; McKindsey, Christopher W; Archambault, Philippe

    2015-01-01

    This experimental microcosm study reports the influence of organic enrichments by mussel biodeposits on the metabolic activity and functional diversity of benthic prokaryotic communities. The different biodeposit enrichment regimes created, which mimicked the quantity of faeces and pseudo-faeces potentially deposited below mussel farms, show a clear stimulatory effect of this organic enrichment on prokaryotic metabolic activity. This effect was detected once a certain level of biodeposition was attained with a tipping point estimated between 3.25 and 10 g day-1 m-2. Prokaryotic communities recovered their initial metabolic activity by 11 days after the cessation of biodeposit additions. However, their functional diversity remained greater than prior to the disturbance suggesting that mussel biodeposit enrichment may disturb the functioning and perhaps the role of prokaryotic communities in benthic ecosystems. This manipulative approach provided new information on the influence of mussel biodeposition on benthic prokaryotic communities and dose-response relationships and may support the development of carrying capacity models for bivalve culture.

  16. Alteration of growth and metabolic activity of cells in the presence of propranolol and metoprolol.

    PubMed

    Lodowska, Jolanta; Wilczok, Adam; Tam, Irena; Cwalina, Beata; Swiatkowska, Longina; Wilczok, Tadeusz

    2003-01-01

    Mechanisms of action at the cellular level of a variety of drugs and xenobiotics may be assessed using Chlorella vulgaris cells. Synchronous culture, which consists of cells at the same phase of development, provides the most convenient model for studying processes at the cellular level. Stability of metabolic activity of synchronously growing cells is achieved by conducting cell culturing under strictly controlled conditions. The aim of the present study was to determine to what extent propranolol and metoprolol alter the Chlorella vulgaris metabolic activity, expressed by the number of progeny cells, the culture absorbance at lambda = 680 nm and the amount of selected photosynthetic pigments (chlorophyll a, chlorophyll b, antheraxanthin, lutein, violaxanthin and beta-carotene). Three different concentrations (10(-4), 10(-5) and 10(-6) M) of propranolol and metoprolol were administered to the Chlorella vulgaris cultures. It has been demonstrated that the higher the propranolol and metoprolol concentrations (from 10(-6) M to 10(-4) M) the lower the number of progeny cells in the cultures, expressed by the lower values of division coefficient. Both the propranolol and metoprolol caused a decrease in the photosynthetic pigments production in the mother cells. This effect was more important in the propranolol-treated cultures. The higher values of photosynthetic pigments concentrations in the progeny cells grown under the presence of a drug indicate that both the drugs tested influence mainly the cell growth and in a lower manner--their metabolic activity, expressed by the production of photosynthetic pigments.

  17. Metabolic activity and genetic diversity of microbial communities inhabiting the rhizosphere of halophyton plants.

    PubMed

    Bárány, Agnes; Szili-Kovács, Tibor; Krett, Gergely; Füzy, Anna; Márialigeti, Károly; Borsodi, Andrea K

    2014-09-01

    A preliminary study was conducted to compare the community level physiological profile (CLPP) and genetic diversity of rhizosphere microbial communities of four plant species growing nearby Kiskunság soda ponds, namely Böddi-szék, Kelemen-szék and Zab-szék. CLPP was assessed by MicroResp method using 15 different substrates while Denaturing Gradient Gel Electrophoresis (DGGE) was used to analyse genetic diversity of bacterial communities. The soil physical and chemical properties were quite different at the three sampling sites. Multivariate statistics (PCA and UPGMA) revealed that Zab-szék samples could be separated according to their genetic profile from the two others which might be attributed to the geographical location and perhaps the differences in soil physical properties. Böddi-szék samples could be separated from the two others considering the metabolic activity which could be explained by their high salt and low humus contents. The number of bands in DGGE gels was related to the metabolic activity, and positively correlated with soil humus content, but negatively with soil salt content. The main finding was that geographical location, soil physical and chemical properties and the type of vegetation were all important factors influencing the metabolic activity and genetic diversity of rhizosphere microbial communities.

  18. Self-Reported Sitting Time, Physical Activity and Fibrinolytic and Other Novel Cardio-Metabolic Biomarkers in Active Swedish Seniors

    PubMed Central

    Howard, Bethany J.; Hurtig-Wennlöf, Anita; Olsson, Lovisa A.; Nilsson, Torbjörn K.; Dunstan, David W.; Wennberg, Patrik

    2016-01-01

    Background Too much sitting is linked with an increased risk of cardiovascular disease and mortality. The mediating mechanisms for these associations are largely unknown, however dysregulated fibrinolysis have emerged as a possible contributor. Objective We examined the associations of self-reported overall sitting time and physical activity with fibrinolytic and other novel cardio-metabolic biomarkers in older adults. Materials and Methods Data was analysed for 364 participants (74±7 yrs) of the Active Seniors group (retired, living independently in their own homes). Linear regression analyses examined associations of categories of categories of sitting time (≤3, 3–6, >6 hrs/day) and overall physical activity (Low, Moderate and High) with biomarkers in serum or plasma, adjusting for age, gender and smoking (with further adjustment for either overall physical activity or sitting time and BMI in secondary analyses). Results Compared to sitting ≤ 3 hrs/day, sitting >6 hrs/day was associated with higher tissue plasminogen activator (tPA) and tissue plasminogen activator/plasminogen activator inhibitor-1 complex (tPA-PAI-1 complex). These associations were not independent of overall physical activity or BMI. Compared to those in the high physical activity, low physical activity was associated with a higher BMI, high-sensitivity C-reactive protein (hs-CRP) and tPA-PAI-1 complex levels. Only the associations of BMI and hs-CRP were independent of sitting time. Conclusions These findings provide preliminary cross-sectional evidence for the relationships of sitting time with fibrinolytic markers in older adults. They also reinforce the importance of regular physical activity for cardio-metabolic health. PMID:27658041

  19. Metabolic Benefit of Chronic Caloric Restriction and Activation of Hypothalamic AGRP/NPY Neurons in Male Mice Is Independent of Ghrelin.

    PubMed

    Rogers, Nicole H; Walsh, Heidi; Alvarez-Garcia, Oscar; Park, Seongjoon; Gaylinn, Bruce; Thorner, Michael O; Smith, Roy G

    2016-04-01

    Aging is associated with attenuated ghrelin signaling. During aging, chronic caloric restriction (CR) produces health benefits accompanied by enhanced ghrelin production. Ghrelin receptor (GH secretagogue receptor 1a) agonists administered to aging rodents and humans restore the young adult phenotype; therefore, we tested the hypothesis that the metabolic benefits of CR are mediated by endogenous ghrelin. Three month-old male mice lacking ghrelin (Ghrelin-/-) or ghrelin receptor (Ghsr-/-), and their wild-type (WT) littermates were randomly assigned to 2 groups: ad libitum (AL) fed and CR, where 40% food restriction was introduced gradually to allow Ghrelin-/- and Ghsr-/- mice to metabolically adapt and avoid severe hypoglycemia. Twelve months later, plasma ghrelin, metabolic parameters, ambulatory activity, hypothalamic and liver gene expression, as well as body composition were measured. CR increased plasma ghrelin and des-acyl ghrelin concentrations in WT and Ghsr-/- mice. CR of WT, Ghsr-/-, and Ghrelin-/- mice markedly improved metabolic flexibility, enhanced ambulatory activity, and reduced adiposity. Inactivation of Ghrelin or Ghsr had no effect on AL food intake or food anticipatory behavior. In contrast to the widely held belief that endogenous ghrelin regulates food intake, CR increased expression of hypothalamic Agrp and Npy, with reduced expression of Pomc across genotypes. In the AL context, ablation of ghrelin signaling markedly inhibited liver steatosis, which correlated with reduced Pparγ expression and enhanced Irs2 expression. Although CR and administration of GH secretagogue receptor 1a agonists both benefit the aging phenotype, we conclude the benefits of chronic CR are a consequence of enhanced metabolic flexibility independent of endogenous ghrelin or des-acyl ghrelin signaling.

  20. Contribution of diet and physical activity to metabolic parameters among survivors of childhood leukemia

    PubMed Central

    Tonorezos, Emily S.; Robien, Kim; Eshelman-Kent, Debra; Moskowitz, Chaya S.; Church, Timothy S.; Ross, Robert; Oeffinger, Kevin C.

    2012-01-01

    Purpose Determine the relationship between diet and metabolic abnormalities among adult survivors of childhood acute lymphoblastic leukemia (ALL). Methods We surveyed 117 adult survivors of childhood ALL using the Harvard Food Frequency Questionnaire. Physical activity energy expenditure (PAEE) was measured with the SenseWear Pro2 Armband. Insulin resistance was estimated using the Homeostasis Model for Insulin Resistance (HOMA-IR). Visceral and subcutaneous adiposity were measured by abdominal CT. Adherence to a Mediterranean diet pattern was calculated using the index developed by Trichopoulou. Subjects were compared using multivariate analysis adjusted for age and gender. Results Greater adherence to a Mediterranean diet pattern was associated with lower visceral adiposity (P=0.07), subcutaneous adiposity (P<0.001), waist circumference (P=0.005), and body mass index (P=0.04). For each point higher on the Mediterranean Diet Score, the odds of having the metabolic syndrome fell by 31% (OR 0.69; 95% CI 0.50, 0.94; P = 0.019). Higher dairy intake was associated with higher HOMA-IR (P =0.014), but other individual components of the Mediterranean diet, such as low intake of meat or high intake of fruits and vegetables, were not significant. PAEE was not independently associated with metabolic outcomes, although higher PAEE was associated with lower body mass index. Conclusions Adherence to a Mediterranean diet pattern was associated with better metabolic and anthropometric parameters in this cross-sectional study of ALL survivors. PMID:23187859

  1. Activated sludge filterability improvement by nitrifying bacteria abundance regulation in an adsorption membrane bioreactor (Ad-MBR).

    PubMed

    Sun, Fei-yun; Lv, Xiao-mei; Li, Ji; Peng, Zhong-yi; Li, Pu; Shao, Ming-fei

    2014-10-01

    Autotrophic nitrifying bacteria have its intrinsic properties including low EPS production, dense colonial structure and slow-growth rate, favoring the sludge filterability improvement. An adsorption-MBR (Ad-MBR) was developed to enrich nitrifier abundance in the MBR chamber by inlet C/N regulation, and its possible positive effect on sludge filterability and underlying mechanisms were investigated. By DNA extraction, PCR amplification and Illumina high-throughput pyrosequencing, the abundance of nitrifying bacteria was accurately quantified. More than 8.29% nitrifier abundance was achieved in Ad-MBR sludge, which was above three times of that in conventional MBR. Regulated C/N ratio and thereafter nitrifier abundance enrichment improved sludge filterability by altering sludge mixture and its supernatant properties, reflected by a good sludge settleability, a low supernatant viscosity and turbidity, a low supernatant organic substances concentration, and a small amount of strong hydrophobic fractional components, thus to profoundly improve sludge filterability and decelerate membrane fouling.

  2. Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites.

    PubMed

    Blevins-Primeau, Andrea S; Sun, Dongxiao; Chen, Gang; Sharma, Arun K; Gallagher, Carla J; Amin, Shantu; Lazarus, Philip

    2009-03-01

    Tamoxifen (TAM) is a selective estrogen receptor modulator widely used in the prevention and treatment of breast cancer. A major mode of metabolism of the major active metabolites of TAM, 4-OH-TAM and endoxifen, is by glucuronidation via the UDP-glucuronosyltransferase (UGT) family of enzymes. To examine whether polymorphisms in the UGT enzymes responsible for the glucuronidation of active TAM metabolites play an important role in interindividual differences in TAM metabolism, cell lines overexpressing wild-type or variant UGTs were examined for their activities against TAM metabolites in vitro. For variants of active extrahepatic UGTs, the UGT1A8(173Ala/277Tyr) variant exhibited no detectable glucuronidation activity against the trans isomers of either 4-OH-TAM or endoxifen. Little or no difference in TAM glucuronidating activity was observed for the UGT1A8(173Gly/277Cys) or UGT1A10(139Lys) variants compared with their wild-type counterparts. For active hepatic UGTs, the UGT2B7(268Tyr) variant exhibited significant (P < 0.01) 2- and 5-fold decreases in activity against the trans isomers of 4-OH-TAM and endoxifen, respectively, compared with wild-type UGT2B7(268His). In studies of 111 human liver microsomal specimens, the rate of O-glucuronidation against trans-4-OH-TAM and trans-endoxifen was 28% (P < 0.001) and 27% (P = 0.002) lower, respectively, in individuals homozygous for the UGT2B7 Tyr(268)Tyr genotype compared with subjects with the UGT2B7 His(268)His genotype, with a significant (P < 0.01) trend of decreasing activity against both substrates with increasing numbers of the UGT2B7(268His) allele. These results suggest that functional polymorphisms in TAM-metabolizing UGTs, including UGT2B7 and potentially UGT1A8, may be important in interindividual variability in TAM metabolism and response to TAM therapy.

  3. Evolution of a new chlorophyll metabolic pathway driven by the dynamic changes in enzyme promiscuous activity.

    PubMed

    Ito, Hisashi; Tanaka, Ayumi

    2014-03-01

    Organisms generate an enormous number of metabolites; however, the mechanisms by which a new metabolic pathway is acquired are unknown. To elucidate the importance of promiscuous enzyme activity for pathway evolution, the catalytic and substrate specificities of Chl biosynthetic enzymes were examined. In green plants, Chl a and Chl b are interconverted by the Chl cycle: Chl a is hydroxylated to 7-hydroxymethyl chlorophyll a followed by the conversion to Chl b, and both reactions are catalyzed by chlorophyllide a oxygenase. Chl b is reduced to 7-hydroxymethyl chlorophyll a by Chl b reductase and then converted to Chl a by 7-hydroxymethyl chlorophyll a reductase (HCAR). A phylogenetic analysis indicated that HCAR evolved from cyanobacterial 3,8-divinyl chlorophyllide reductase (DVR), which is responsible for the reduction of an 8-vinyl group in the Chl biosynthetic pathway. In addition to vinyl reductase activity, cyanobacterial DVR also has Chl b reductase and HCAR activities; consequently, three of the four reactions of the Chl cycle already existed in cyanobacteria, the progenitor of the chloroplast. During the evolution of cyanobacterial DVR to HCAR, the HCAR activity, a promiscuous reaction of cyanobacterial DVR, became the primary reaction. Moreover, the primary reaction (vinyl reductase activity) and some disadvantageous reactions were lost, but the neutral promiscuous reaction (NADH dehydrogenase) was retained in both DVR and HCAR. We also show that a portion of the Chl c biosynthetic pathway already existed in cyanobacteria. We discuss the importance of dynamic changes in promiscuous activity and of the latent pathways for metabolic evolution.

  4. Activities of nitrate reductase and glutamine synthetase in rice seedlings during cyanide metabolism.

    PubMed

    Yu, Xiao-Zhang; Zhang, Fu-Zhong

    2012-07-30

    A study was conducted to investigate activities of nitrate reductase (NR) and glutamine synthetase (GS) in plants during cyanide metabolism. Young rice seedlings (Oryza sativa L. cv. XZX 45) were grown in the nutrient solutions containing KNO(3) or NH(4)Cl and treated with free cyanide (KCN). Cyanide in solutions and in plant materials was analyzed to estimate the phyto-assimilation potential. Activities of NR and GS in different parts of rice seedlings were assayed in vivo. Seedlings grown on NH(4)(+) showed significantly higher relative growth rate than those on NO(3)(-) (p<0.05) in the presence of exogenous cyanide. The metabolic rates of cyanide by seedlings were all positively correlated to the concentrations supplied. A negligible difference was observed between the two treatments with nitrate and ammonium (p>0.05). Enzymatic assays showed that cyanide (≥0.97mg CN L(-1)) impaired NR activity significantly in both roots and shoots (p<0.05). The effect of cyanide on GS activity in roots was more evident at 1.93mg CN L(-1), suggesting that NR activity was more susceptible to change from cyanide application than GS activity. The results observed here suggest that the exogenous cyanide, which to a certain level has a beneficial role in plant nutrition.

  5. SIRT4 has tumor suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism

    PubMed Central

    Jeong, Seung Min; Xiao, Cuiying; Finley, Lydia W.S; Lahusen, Tyler; Souza, Amanda L.; Pierce, Kerry; Li, Ying-Hua; Wang, Xiaoxu; Laurent, Gaëlle; German, Natalie J.; Xu, Xiaoling; Li, Cuiling; Wang, Rui-Hong; Lee, Jaewon; Csibi, Alfredo; Cerione, Richard; Blenis, John; Clish, Clary B.; Kimmelman, Alec; Deng, Chu-Xia; Haigis, Marcia C.

    2013-01-01

    SUMMARY DNA damage elicits a cellular signaling response that initiates cell cycle arrest and DNA repair. Here we find that DNA damage triggers a critical block in glutamine metabolism, which is required for proper DNA damage responses. This block requires the mitochondrial SIRT4, which is induced by numerous genotoxic agents and represses the metabolism of glutamine into TCA cycle. SIRT4 loss leads to both increased glutamine-dependent proliferation and stress-induced genomic instability, resulting in tumorigenic phenotypes. Moreover, SIRT4 knockout mice spontaneously develop lung tumors. Our data uncover SIRT4 as an important component of the DNA damage response pathway that orchestrates a metabolic block in glutamine metabolism, cell cycle arrest and tumor suppression. PMID:23562301

  6. A column level, low power, 1 M sample/s double ramp A/D converter for monolithic active pixel sensors in high energy physics

    NASA Astrophysics Data System (ADS)

    Pillet, N.; Heini, S.; Hu, Y.

    2010-08-01

    Monolithic active pixel sensors (MAPS) using standard low cost CMOS technologies available from industrial manufacturers have demonstrated excellent tracking performances for minimum ionizing particles. The need for highly granular, fast, thin sensors with a full digital output drives an R&D effort, aiming to design and optimize a low power high speed A/D converter integrated at the column level. Following this main issue, a double digital ramp A/D converter has been proposed for CMOS monolithic active pixel sensors in this paper. This A/D converter responds to the constraints of size, power dissipation and precision for CMOS sensors for particle detection. It also represents a first step in order to reach the high speed of conversion needed for this kind of application. The A/D converter has a resolution of 4 bits for conversion speed of 1 M sample/s with only 264 μW of static consumption in a very particular pitch of 25 μm×900 μm.

  7. Ad.Egr-TNF and Local Ionizing Radiation Suppress Metastases by Interferon-β-Dependent Activation of Antigen-specific CD8+ T Cells

    PubMed Central

    Meng, Yuru; Mauceri, Helena J; Khodarev, Nikolai N; Darga, Thomas E; Pitroda, Sean P; Beckett, Michael A; Kufe, Donald W; Weichselbaum, Ralph R

    2010-01-01

    Ad.Egr-TNF is a radioinducible adenovector currently in phase 3 trials for inoperable pancreatic cancer. The combination of Ad.Egr-TNF and ionizing radiation (IR) contributes to local tumor control through the production of tumor necrosis factor-α (TNFα) in the tumor microenvironment. Moreover, clinical and preclinical studies with Ad.Egr-TNF/IR have suggested that this local approach suppresses the growth of distant metastatic disease; however, the mechanisms responsible for this effect remain unclear. These studies have been performed in wild-type (WT) and TNFR1,2−/− mice to assess the role of TNFα-induced signaling in the suppression of draining lymph node (DLN) metastases. The results demonstrate that production of TNFα in the tumor microenvironment induces expression of interferon (IFNβ). In turn, IFNβ stimulates the production of chemokines that recruit CD8+ T cells to the tumor. The results further demonstrate that activation of tumor antigen–specific CD8+ CTLs contributes to local antitumor activity and suppression of DLN metastases. These findings support a model in which treatment of tumors with Ad.Egr-TNF and IR is mediated by local and distant immune-mediated antitumor effects that suppress the development of metastases. PMID:20197756

  8. Metabolic brain activity suggestive of persistent pain in a rat model of neuropathic pain

    PubMed Central

    Thompson, Scott J; Millecamps, Magali; Aliaga, Antonio; Seminowicz, David A; Low, Lucie A; Bedell, Barry J; Stone, Laura S; Schweinhardt, Petra; Bushnell, M Catherine

    2014-01-01

    Persistent pain is a central characteristic of neuropathic pain conditions in humans. Knowing whether rodent models of neuropathic pain produce persistent pain is therefore crucial to their translational applicability. We investigated the Spared Nerve Injury (SNI) model of neuropathic pain and the formalin pain model in rats using Positron Emission Tomography (PET) with the metabolic tracer [18F]fluorodeoxyglucose (FDG) to determine if there is ongoing brain activity suggestive of persistent pain. For the formalin model, under brief anesthesia we injected one hindpaw with 5% formalin and the FDG tracer into a tail vein. We then allowed the animals to awaken and observed pain behavior for 30 min during the FDG uptake period. The rat was then anesthetized and placed in the scanner for static image acquisition, which took place between minutes 45 and 75 post-tracer injection. A single reference rat brain magnetic resonance image (MRI) was used to align the PET images with the Paxinos and Watson rat brain atlas. Increased glucose metabolism was observed in the somatosensory region associated with the injection site (S1 hindlimb contralateral), S1 jaw/upper lip and cingulate cortex. Decreases were observed in the prelimbic cortex and hippocampus. Second, SNI rats were scanned 3 weeks post-surgery using the same scanning paradigm, and region-of-interest analyses revealed increased metabolic activity in the contralateral S1 hindlimb. Finally, a second cohort of SNI rats were scanned while anesthetized during the tracer uptake period, and the S1 hindlimb increase was not observed. Increased brain activity in the somatosensory cortex of SNI rats resembled the activity produced with the injection of formalin, suggesting that the SNI model may produce persistent pain. The lack of increased activity in S1 hindlimb with general anesthetic demonstrates that this effect can be blocked, as well as highlights the importance of investigating brain activity in awake and behaving

  9. Metabolic brain activity suggestive of persistent pain in a rat model of neuropathic pain.

    PubMed

    Thompson, Scott J; Millecamps, Magali; Aliaga, Antonio; Seminowicz, David A; Low, Lucie A; Bedell, Barry J; Stone, Laura S; Schweinhardt, Petra; Bushnell, M Catherine

    2014-05-01

    Persistent pain is a central characteristic of neuropathic pain conditions in humans. Knowing whether rodent models of neuropathic pain produce persistent pain is therefore crucial to their translational applicability. We investigated the spared nerve injury (SNI) model of neuropathic pain and the formalin pain model in rats using positron emission tomography (PET) with the metabolic tracer [18F]fluorodeoxyglucose (FDG) to determine if there is ongoing brain activity suggestive of persistent pain. For the formalin model, under brief anesthesia we injected one hindpaw with 5% formalin and the FDG tracer into a tail vein. We then allowed the animals to awaken and observed pain behavior for 30min during the FDG uptake period. The rat was then anesthetized and placed in the scanner for static image acquisition, which took place between minutes 45 and 75 post-tracer injection. A single reference rat brain magnetic resonance image (MRI) was used to align the PET images with the Paxinos and Watson rat brain atlas. Increased glucose metabolism was observed in the somatosensory region associated with the injection site (S1 hindlimb contralateral), S1 jaw/upper lip and cingulate cortex. Decreases were observed in the prelimbic cortex and hippocampus. Second, SNI rats were scanned 3weeks post-surgery using the same scanning paradigm, and region-of-interest analyses revealed increased metabolic activity in the contralateral S1 hindlimb. Finally, a second cohort of SNI rats was scanned while anesthetized during the tracer uptake period, and the S1 hindlimb increase was not observed. Increased brain activity in the somatosensory cortex of SNI rats resembled the activity produced with the injection of formalin, suggesting that the SNI model may produce persistent pain. The lack of increased activity in S1 hindlimb with general anesthetic demonstrates that this effect can be blocked, as well as highlights the importance of investigating brain activity in awake and behaving rodents.

  10. Metabolic Activation of the Anti-Hepatitis C Virus Nucleotide Prodrug PSI-352938

    PubMed Central

    Niu, Congrong; Tolstykh, Tatiana; Bao, Haiying; Park, Yeojin; Babusis, Darius; Lam, Angela M.; Bansal, Shalini; Du, Jinfa; Chang, Wonsuk; Reddy, P. Ganapati; Zhang, Hai-Ren; Woolley, Joseph; Wang, Li-Quan; Chao, Piyun B.; Ray, Adrian S.; Otto, Michael J.; Sofia, Michael J.

    2012-01-01

    PSI-352938 is a novel cyclic phosphate prodrug of β-d-2′-deoxy-2′-α-fluoro-2′-β-C-methylguanosine-5′-monophosphate with potent anti-HCV activity. In order to inhibit the NS5B RNA-dependent RNA polymerase, PSI-352938 must be metabolized to the active triphosphate form, PSI-352666. During in vitro incubations with PSI-352938, significantly larger amounts of PSI-352666 were formed in primary hepatocytes than in clone A hepatitis C virus (HCV) replicon cells. Metabolism and biochemical assays were performed to define the molecular mechanism of PSI-352938 activation. The first step, removal of the isopropyl group on the 3′,5′-cyclic phosphate moiety, was found to be cytochrome P450 (CYP) 3A4 dependent, with other CYP isoforms unable to catalyze the reaction. The second step, opening of the cyclic phosphate ring, was catalyzed by phosphodiesterases (PDEs) 2A1, 5A, 9A, and 11A4, all known to be expressed in the liver. The role of these enzymes in the activation of PSI-352938 was confirmed in primary human hepatocytes, where prodrug activation was reduced by inhibitors of CYP3A4 and PDEs. The third step, removal of the O6-ethyl group on the nucleobase, was shown to be catalyzed by adenosine deaminase-like protein 1. The resulting monophosphate was consecutively phosphorylated to the diphosphate and to the triphosphate PSI-352666 by guanylate kinase 1 and nucleoside diphosphate kinase, respectively. In addition, formation of nucleoside metabolites was observed in primary hepatocytes, and ecto-5′-nucleotidase was able to dephosphorylate the monophosphate metabolites. Since CYP3A4 is highly expressed in the liver, the CYP3A4-dependent metabolism of PSI-352938 makes it an effective liver-targeted prodrug, in part accounting for the potent antiviral activity observed clinically. PMID:22526308

  11. Effect of contrasted levels of habitual physical activity on metabolic flexibility.

    PubMed

    Bergouignan, Audrey; Antoun, Edwina; Momken, Iman; Schoeller, Dale A; Gauquelin-Koch, Guillemette; Simon, Chantal; Blanc, Stéphane

    2013-02-01

    The factors regulating the body's ability to switch from fat to carbohydrate oxidation in response to fuel availability changes, or metabolic flexibility (MF), are currently intensively investigated in the context of metabolic diseases. Although numerous metabolic diseases are associated with sedentary behaviors and metabolic inflexibility, the effect of habitual physical activity level (PAL) on MF regulation is surprisingly poorly known. We investigated how PAL affects MF in cross-sectional and interventional studies. MF was assessed in 44 subjects: normal-weight and overweight sedentary men submitted to 2 mo of exercise at current recommendations, normal-weight active men submitted to 1 mo of reduced PAL and normal-weight women submitted to 1 mo of bed rest, with or without exercise. MF was evaluated, before and after interventions, following two standard meals as the relationship between individual mathematical variances in insulin and nonprotein respiratory quotient (NPRQ) daily kinetics. Daily NPRQ and insulin variances differed according to habitual PAL (P = 0.002 and P = 0.009, respectively); active subjects had higher variances in NPRQ for lower variances in insulin than sedentary subjects, indicating a better MF. Detraining increased insulin variance (P = 0.009) and decreased NPRQ variance (P = 0.003), while training tended to have opposite effects. Insulin and NPRQ variances were negatively related along the PAL continuum (R(2) = 0.70, P < 0.001). Variance in NPRQ was also positively related to PAL (R(2) = 0.52, P < 0.001). By assessing MF with mathematical surrogates in conditions of daily pattern in meal's intake, we showed that habitual PAL is associated with MF status, and that MF is modulated by changes in PAL.

  12. Activation of an Otherwise Silent Xylose Metabolic Pathway in Shewanella oneidensis

    PubMed Central

    Sekar, Ramanan; Shin, Hyun Dong

    2016-01-01

    ABSTRACT Shewanella oneidensis is unable to metabolize the sugar xylose as a carbon and energy source. In the present study, an otherwise silent xylose catabolic pathway was activated in S. oneidensis by following an adaptive evolution strategy. Genome-wide scans indicated that the S. oneidensis genome encoded two proteins similar to the xylose oxido-reductase pathway enzymes xylose reductase (SO_0900) and xylulokinase (SO_4230), and purified SO_0900 and SO_4230 displayed xylose reductase and xylulokinase activities, respectively. The S. oneidensis genome was missing, however, an Escherichia coli XylE-like xylose transporter. After 12 monthly transfers in minimal growth medium containing successively higher xylose concentrations, an S. oneidensis mutant (termed strain XM1) was isolated for the acquired ability to grow aerobically on xylose as a carbon and energy source. Whole-genome sequencing indicated that strain XM1 contained a mutation in an unknown membrane protein (SO_1396) resulting in a glutamine-to-histidine conversion at amino acid position 207. Homology modeling demonstrated that the Q207H mutation in SO_1396 was located at the homologous xylose docking site in XylE. The expansion of the S. oneidensis metabolic repertoire to xylose expands the electron donors whose oxidation may be coupled to the myriad of terminal electron-accepting processes catalyzed by S. oneidensis. Since xylose is a lignocellulose degradation product, this study expands the potential substrates to include lignocellulosic biomass. IMPORTANCE The activation of an otherwise silent xylose metabolic system in Shewanella oneidensis is a powerful example of how accidental mutations allow microorganisms to adaptively evolve. The expansion of the S. oneidensis metabolic repertoire to xylose expands the electron donors whose oxidation may be coupled to the myriad of terminal electron-accepting processes catalyzed by S. oneidensis. Since xylose is a lignocellulose degradation product, this

  13. Compartment-specific activation of PPARγ governs breast cancer tumor growth, via metabolic reprogramming and symbiosis.

    PubMed

    Avena, Paola; Anselmo, Wanda; Whitaker-Menezes, Diana; Wang, Chenguang; Pestell, Richard G; Lamb, Rebecca S; Hulit, James; Casaburi, Ivan; Andò, Sebastiano; Martinez-Outschoorn, Ubaldo E; Lisanti, Michael P; Sotgia, Federica

    2013-05-01

    The role of PPARγ in cancer therapy is controversial, with studies showing either pro-tumorigenic or antineoplastic effects. This debate is very clinically relevant, because PPARγ agonists are used as antidiabetic drugs. Here, we evaluated if the effects of PPARγ on tumorigenesis are determined by the cell type in which PPARγ is activated. Second, we examined if the metabolic changes induced by PPARγ, such as glycolysis and autophagy, play any role in the tumorigenic process. To this end, PPARγ was overexpressed in breast cancer cells or in stromal cells. PPARγ-overexpressing cells were examined with respect to (1) their tumorigenic potential, using xenograft models, and (2) regarding their metabolic features. In xenograft models, we show that when PPARγ is activated in cancer cells, tumor growth is inhibited by 40%. However, when PPARγ is activated in stromal cells, the growth of co-injected breast cancer cells is enhanced by 60%. Thus, the effect(s) of PPARγ on tumorigenesis are dependent on the cell compartment in which PPARγ is activated. Mechanistically, stromal cells with activated PPARγ display metabolic features of cancer-associated fibroblasts, with increased autophagy, glycolysis and senescence. Indeed, fibroblasts overexpressing PPARγ show increased expression of autophagic markers, increased numbers of acidic autophagic vacuoles, increased production of L-lactate, cell hypertrophy and mitochondrial dysfunction. In addition, PPARγ fibroblasts show increased expression of CDKs (p16/p21) and β-galactosidase, which are markers of cell cycle arrest and senescence. Finally, PPARγ induces the activation of the two major transcription factors that promote autophagy and glycolysis, i.e., HIF-1α and NFκB, in stromal cells. Thus, PPARγ activation in stromal cells results in the formation of a catabolic pro-inflammatory microenvironment that metabolically supports cancer growth. Interestingly, the tumor inhibition observed when PPARγ is

  14. Intraspecific variation in aerobic metabolic rate of fish: relations with organ size and enzyme activity in brown trout.

    PubMed

    Norin, Tommy; Malte, Hans

    2012-01-01

    Highly active animals require a high aerobic capacity (i.e., a high maximum metabolic rate [MMR]) to sustain such activity, and it has been speculated that a greater capacity for aerobic performance is reflected in larger organs, which serve as energy processors but are also expensive to maintain and which increase the minimal cost of living (i.e., the basal or standard metabolic rate [SMR]). In this study, we assessed the extent of intraspecific variation in metabolic rate within a group of brown trout (Salmo trutta L.) and tested whether the observed variation in residual (body-mass-corrected) SMR, MMR, and absolute aerobic scope could be explained by variations in the residual size (mass) of metabolically active internal organs. Residual SMR was found to correlate positively with residual MMR, indicating a link between these two metabolic parameters, but no relationship between organ mass and metabolic rate was found for liver, heart, spleen, intestine, or stomach. Instead, activity in the liver of two aerobic mitochondrial enzymes, cytochrome c oxidase and, to a lesser extent, citrate synthase, was found to correlate with whole-animal metabolic rate, indicating that causes for intraspecific variation in the metabolic rate of fish can be found at a lower organizational level than organ size.

  15. [Important application of intestinal transporters and metabolism enzymes on gastrointestinal disposal of active ingredients of Chinese materia medica].

    PubMed

    Bi, Xiaolin; Du, Qiu; Di, Liuqing

    2010-02-01

    Oral drug bioavailability depends on gastrointestinal absorption, intestinal transporters and metabolism enzymes are the important factors in drug gastrointestinal absorption and they can also be induced or inhibited by the active ingredients of Chinese materia medica. This article presents important application of intestinal transporters and metabolism enzymes on gastrointestinal disposal of the active ingredients of Chinese materia medica, and points out the importance of research on transport and metabolism of the active ingredients of Chinese materia medica in Chinese extract and Chinese medicinal formulae.

  16. Influence of uranium (VI) on the metabolic activity of stable multispecies biofilms studied by oxygen microsensors and fluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Krawczyk-Bärsch, Evelyn; Grossmann, Kay; Arnold, Thuro; Hofmann, Susann; Wobus, Axel

    2008-11-01

    The effect of uranium added in ecologically relevant concentrations (1 × 10 -5 and 1 × 10 -6 M) to stable multispecies biofilms was studied by electrochemical oxygen microsensors with tip diameters of 10 μm and by confocal laser fluorescence microscopy (CLSM). The microsensor profile measurements in the stable multispecies biofilms exposed to uranium showed that the oxygen concentration decreased faster with increasing biofilm depth compared to the uranium free biofilms. In the uranium containing biofilms, the oxygen consumption, calculated from the steady-state microprofiles, showed high consumption rates of up to 61.7 nmol cm -3 s -1 in the top layer (0-70 μm) and much lower consumption rates in the lower zone of the biofilms. Staining experiments with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and 4,6-diamidino-2-phenylindole (DAPI) confirmed the high respiratory activities of the bacteria in the upper layer. Analysis of the amplified 16S rRNA gene fragments showed that the addition of uranium in ecologically relevant concentrations did not change the bacterial diversity in the stable multispecies biofilms and is therefore not responsible for the different oxygen profiles in the biofilms. The fast decrease in the oxygen concentrations in the biofilm profiles showed that the bacteria in the top region of the biofilms, i.e., the metabolically most active biofilm zone, battle the toxic effects of aqueous uranium with an increased respiratory activity. This increased respiratory activity results in O 2 depleted zones closer to the biofilm/air interface which may trigger uranium redox processes, since suitable redox partners, e.g., extracellular polymeric substance (EPS) and other organics (e.g., metabolites), are sufficiently available in the biofilm porewaters. Such redox reactions may lead to precipitation of uranium (IV) solids and consequently to a removal of uranium from the aqueous phase.

  17. Triclocarban Mediates Induction of Xenobiotic Metabolism through Activation of the Constitutive Androstane Receptor and the Estrogen Receptor Alpha

    PubMed Central

    Yueh, Mei-Fei; Li, Tao; Evans, Ronald M.; Hammock, Bruce; Tukey, Robert H.

    2012-01-01

    Triclocarban (3,4,4′-trichlorocarbanilide, TCC) is used as a broad-based antimicrobial agent that is commonly added to personal hygiene products. Because of its extensive use in the health care industry and resistance to degradation in sewage treatment processes, TCC has become a significant waste product that is found in numerous environmental compartments where humans and wildlife can be exposed. While TCC has been linked to a range of health and environmental effects, few studies have been conducted linking exposure to TCC and induction of xenobiotic metabolism through regulation by environmental sensors such as the nuclear xenobiotic receptors (XenoRs). To identify the ability of TCC to activate xenobiotic sensors, we monitored XenoR activities in response to TCC treatment using luciferase-based reporter assays. Among the XenoRs in the reporter screening assay, TCC promotes both constitutive androstane receptor (CAR) and estrogen receptor alpha (ERα) activities. TCC treatment to hUGT1 mice resulted in induction of the UGT1A genes in liver. This induction was dependent upon the constitutive active/androstane receptor (CAR) because no induction occurred in hUGT1Car−/− mice. Induction of the UGT1A genes by TCC corresponded with induction of Cyp2b10, another CAR target gene. TCC was demonstrated to be a phenobarbital-like activator of CAR in receptor-based assays. While it has been suggested that TCC be classified as an endocrine disruptor, it activates ERα leading to induction of Cyp1b1 in female ovaries as well as in promoter activity. Activation of ERα by TCC in receptor-based assays also promotes induction of human CYP2B6. These observations demonstrate that TCC activates nuclear xenobiotic receptors CAR and ERα both in vivo and in vitro and might have the potential to alter normal physiological homeostasis. Activation of these xenobiotic-sensing receptors amplifies gene expression profiles that might represent a mechanistic base for potential human

  18. Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.

    PubMed

    Agarwal, Varsha; Kommaddi, Reddy P; Valli, Khader; Ryder, Daniel; Hyde, Thomas M; Kleinman, Joel E; Strobel, Henry W; Ravindranath, Vijayalakshmi

    2008-06-11

    Cytochrome P450 (P450) is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP) in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP) is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP) while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.

  19. Transcriptional activity of the giant barrel sponge, Xestospongia muta Holobiont: molecular evidence for metabolic interchange

    PubMed Central

    Fiore, Cara L.; Labrie, Micheline; Jarett, Jessica K.; Lesser, Michael P.

    2015-01-01

    Compared to our understanding of the taxonomic composition of the symbiotic microbes in marine sponges, the functional diversity of these symbionts is largely unknown. Furthermore, the application of genomic, transcriptomic, and proteomic techniques to functional questions on sponge host-symbiont interactions is in its infancy. In this study, we generated a transcriptome for the host and a metatranscriptome of its microbial symbionts for the giant barrel sponge, Xestospongia muta, from the Caribbean. In combination with a gene-specific approach, our goals were to (1) characterize genetic evidence for nitrogen cycling in X. muta, an important limiting nutrient on coral reefs (2) identify which prokaryotic symbiont lineages are metabolically active and, (3) characterize the metabolic potential of the prokaryotic community. Xestospongia muta expresses genes from multiple nitrogen transformation pathways that when combined with the abundance of this sponge, and previous data on dissolved inorganic nitrogen fluxes, shows that this sponge is an important contributor to nitrogen cycling biogeochemistry on coral reefs. Additionally, we observed significant differences in gene expression of the archaeal amoA gene, which is involved in ammonia oxidation, between coral reef locations consistent with differences in the fluxes of dissolved inorganic nitrogen previously reported. In regards to symbiont metabolic potential, the genes in the biosynthetic pathways of several amino acids were present in the prokaryotic metatranscriptome dataset but in the host-derived transcripts only the catabolic reactions for these amino acids were present. A similar pattern was observed for the B vitamins (riboflavin, biotin, thiamin, cobalamin). These results expand our understanding of biogeochemical cycling in sponges, and the metabolic interchange highlighted here advances the field of symbiont physiology by elucidating specific metabolic pathways where there is high potential for host

  20. Irregular 24-hour Activity Rhythms and the Metabolic Syndrome in Older Adults

    PubMed Central

    Sohail, Shahmir; Yu, Lei; Bennett, David A.; Buchman, Aron S.; Lim, Andrew S.P.

    2015-01-01

    Circadian rhythms – near 24-hour intrinsic biological rhythms – modulate many aspects of human physiology and hence disruption of circadian rhythms may have an important impact on human health. Experimental work supports a potential link between irregular circadian rhythms and several key risk factors for cardiovascular disease including hypertension, obesity, diabetes, and dyslipidemia, collectively termed the metabolic syndrome. While several epidemiological studies have demonstrated an association between shift-work and the components of the metabolic syndrome in working-age adults, there is a relative paucity of data concerning the impact of non-occupational circadian irregularity in older women and men. To address this question, we studied 7 days of actigraphic data from 1137 older woman and men participating in the Rush Memory and Aging Project, a community-based cohort study of the chronic conditions of aging. The regularity of activity rhythms was quantified using the nonparametric interdaily stability metric, and was related to the metabolic syndrome and its components obesity, hypertension, diabetes, and dyslipidemia. More regular activity rhythms were associated with a lower odds of having the metabolic syndrome (OR=0.69, 95%CI=0.60–0.80, p=5.8×10−7), being obese (OR=0.73, 95%CI=0.63–0.85, p=2.5×10−5), diabetic (OR=0.76, 95%CI=0.65–0.90, p=9.3×10−4), hypertensive (OR=0.78, 95%CI=0.66–0.91, p=2.0×10−3), or dyslipidemic (OR=0.82, 95%CI=0.72–0.92, p=1.2×10−3). These associations were independent of differences in objectively measured total daily physical activity or rest, and were not accounted for by prevalent coronary artery disease, stroke, or peripheral artery disease. Moreover, more regular activity rhythms were associated with lower odds of having cardiovascular disease (OR=0.83; 95%CI=0.73–0.95, p=5.7×10−3), an effect that was statistically mediated by the metabolic syndrome. We conclude that irregular activity

  1. Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity

    SciTech Connect

    Pols, Thijs W.H.; Ottenhoff, Roelof; Vos, Mariska; Levels, Johannes H.M.; Quax, Paul H.A.; Meijers, Joost C.M.; Pannekoek, Hans; Groen, Albert K.; Vries, Carlie J.M. de

    2008-02-22

    NR4A nuclear receptors are induced in the liver upon fasting and regulate hepatic gluconeogenesis. Here, we studied the role of nuclear receptor Nur77 (NR4A1) in hepatic lipid metabolism. We generated mice expressing hepatic Nur77 using adenoviral vectors, and demonstrate that these mice exhibit a modulation of the plasma lipid profile and a reduction in hepatic triglyceride. Expression analysis of >25 key genes involved in lipid metabolism revealed that Nur77 inhibits SREBP1c expression. This results in decreased SREBP1c activity as is illustrated by reduced expression of its target genes stearoyl-coA desaturase-1, mitochondrial glycerol-3-phosphate acyltransferase, fatty acid synthase and the LDL receptor, and provides a mechanism for the physiological changes observed in response to Nur77. Expression of LXR target genes Abcg5 and Abcg8 is reduced by Nur77, and may suggest involvement of LXR in the inhibitory action of Nur77 on SREBP1c expression. Taken together, our study demonstrates that Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity.

  2. Transcriptional profiling unravels potential metabolic activities of the olive leaf non-glandular trichome

    PubMed Central

    Koudounas, Konstantinos; Manioudaki, Maria E.; Kourti, Anna; Banilas, Georgios; Hatzopoulos, Polydefkis

    2015-01-01

    The olive leaf trichomes are multicellular peltate hairs densely distributed mainly at the lower leaf epidermis. Although, non-glandular, they have gained much attention since they significantly contribute to abiotic and biotic stress tolerance of olive leaves. The exact mechanisms by which olive trichomes achieve these goals are not fully understood. They could act as mechanical barrier but they also accumulate high amounts of flavonoids among other secondary metabolites. However, little is currently known about the exact compounds they produce and the respective metabolic pathways. Here we present the first EST analysis from olive leaf trichomes by using 454-pyrosequencing. A total of 5368 unigenes were identified out of 7258 high quality reads with an average length of 262 bp. Blast search revealed that 27.5% of them had high homologies to known proteins. By using Blast2GO, 1079 unigenes (20.1%) were assigned at least one Gene Ontology (GO) term. Most of the genes were involved in cellular and metabolic processes and in binding functions followed by catalytic activity. A total of 521 transcripts were mapped to 67 KEGG pathways. Olive trichomes represent a tissue of highly unique transcriptome as per the genes involved in developmental processes and the secondary metabolism. The results indicate that mature olive trichomes are trancriptionally active, mainly through the potential production of enzymes that contribute to phenolic compounds with important roles in biotic and abiotic stress responses. PMID:26322070

  3. Blood flow to long bones indicates activity metabolism in mammals, reptiles and dinosaurs

    PubMed Central

    Seymour, Roger S.; Smith, Sarah L.; White, Craig R.; Henderson, Donald M.; Schwarz-Wings, Daniela

    2012-01-01

    The cross-sectional area of a nutrient foramen of a long bone is related to blood flow requirements of the internal bone cells that are essential for dynamic bone remodelling. Foramen area increases with body size in parallel among living mammals and non-varanid reptiles, but is significantly larger in mammals. An index of blood flow rate through the foramina is about 10 times higher in mammals than in reptiles, and even higher if differences in blood pressure are considered. The scaling of foramen size correlates well with maximum whole-body metabolic rate during exercise in mammals and reptiles, but less well with resting metabolic rate. This relates to the role of blood flow associated with bone remodelling during and following activity. Mammals and varanid lizards have much higher aerobic metabolic rates and exercise-induced bone remodelling than non-varanid reptiles. Foramen areas of 10 species of dinosaur from five taxonomic groups are generally larger than from mammals, indicating a routinely highly active and aerobic lifestyle. The simple measurement holds possibilities offers the possibility of assessing other groups of extinct and living vertebrates in relation to body size, behaviour and habitat. PMID:21733896

  4. Inner workings of thrombolites: spatial gradients of metabolic activity as revealed by metatranscriptome profiling

    NASA Astrophysics Data System (ADS)

    Mobberley, J. M.; Khodadad, C. L. M.; Visscher, P. T.; Reid, R. P.; Hagan, P.; Foster, J. S.

    2015-07-01

    Microbialites are sedimentary deposits formed by the metabolic interactions of microbes and their environment. These lithifying microbial communities represent one of the oldest ecosystems on Earth, yet the molecular mechanisms underlying the function of these communities are poorly understood. In this study, we used comparative metagenomic and metatranscriptomic analyses to characterize the spatial organization of the thrombolites of Highborne Cay, The Bahamas, an actively forming microbialite system. At midday, there were differences in gene expression throughout the spatial profile of the thrombolitic mat with a high abundance of transcripts encoding genes required for photosynthesis, nitrogen fixation and exopolymeric substance production in the upper three mm of the mat. Transcripts associated with denitrification and sulfate reduction were in low abundance throughout the depth profile, suggesting these metabolisms were less active during midday. Comparative metagenomics of the Bahamian thrombolites with other known microbialite ecosystems from across the globe revealed that, despite many shared core pathways, the thrombolites represented genetically distinct communities. This study represents the first time the metatranscriptome of living microbialite has been characterized and offers a new molecular perspective on those microbial metabolisms, and their underlying genetic pathways, that influence the mechanisms of carbonate precipitation in lithifying microbial mat ecosystems.

  5. Blood flow to long bones indicates activity metabolism in mammals, reptiles and dinosaurs.

    PubMed

    Seymour, Roger S; Smith, Sarah L; White, Craig R; Henderson, Donald M; Schwarz-Wings, Daniela

    2012-02-07

    The cross-sectional area of a nutrient foramen of a long bone is related to blood flow requirements of the internal bone cells that are essential for dynamic bone remodelling. Foramen area increases with body size in parallel among living mammals and non-varanid reptiles, but is significantly larger in mammals. An index of blood flow rate through the foramina is about 10 times higher in mammals than in reptiles, and even higher if differences in blood pressure are considered. The scaling of foramen size correlates well with maximum whole-body metabolic rate during exercise in mammals and reptiles, but less well with resting metabolic rate. This relates to the role of blood flow associated with bone remodelling during and following activity. Mammals and varanid lizards have much higher aerobic metabolic rates and exercise-induced bone remodelling than non-varanid reptiles. Foramen areas of 10 species of dinosaur from five taxonomic groups are generally larger than from mammals, indicating a routinely highly active and aerobic lifestyle. The simple measurement holds possibilities offers the possibility of assessing other groups of extinct and living vertebrates in relation to body size, behaviour and habitat.

  6. Inner workings of thrombolites: spatial gradients of metabolic activity as revealed by metatranscriptome profiling

    PubMed Central

    Mobberley, J. M.; Khodadad, C. L. M.; Visscher, P. T.; Reid, R. P.; Hagan, P.; Foster, J. S.

    2015-01-01

    Microbialites are sedimentary deposits formed by the metabolic interactions of microbes and their environment. These lithifying microbial communities represent one of the oldest ecosystems on Earth, yet the molecular mechanisms underlying the function of these communities are poorly understood. In this study, we used comparative metagenomic and metatranscriptomic analyses to characterize the spatial organization of the thrombolites of Highborne Cay, The Bahamas, an actively forming microbialite system. At midday, there were differences in gene expression throughout the spatial profile of the thrombolitic mat with a high abundance of transcripts encoding genes required for photosynthesis, nitrogen fixation and exopolymeric substance production in the upper three mm of the mat. Transcripts associated with denitrification and sulfate reduction were in low abundance throughout the depth profile, suggesting these metabolisms were less active during midday. Comparative metagenomics of the Bahamian thrombolites with other known microbialite ecosystems from across the globe revealed that, despite many shared core pathways, the thrombolites represented genetically distinct communities. This study represents the first time the metatranscriptome of living microbialite has been characterized and offers a new molecular perspective on those microbial metabolisms, and their underlying genetic pathways, that influence the mechanisms of carbonate precipitation in lithifying microbial mat ecosystems. PMID:26213359

  7. Physical activity: benefit or weakness in metabolic adaptations in a mouse model of chronic food restriction?

    PubMed

    Méquinion, Mathieu; Caron, Emilie; Zgheib, Sara; Stievenard, Aliçia; Zizzari, Philippe; Tolle, Virginie; Cortet, Bernard; Lucas, Stéphanie; Prévot, Vincent; Chauveau, Christophe; Viltart, Odile

    2015-02-01

    In restrictive-type anorexia nervosa (AN) patients, physical activity is usually associated with food restriction, but its physiological consequences remain poorly characterized. In female mice, we evaluated the impact of voluntary physical activity with/without chronic food restriction on metabolic and endocrine parameters that might contribute to AN. In this protocol, FRW mice (i.e., food restriction with running wheel) reached a crucial point of body weight loss (especially fat mass) faster than FR mice (i.e., food restriction only). However, in contrast to FR mice, their body weight stabilized, demonstrating a protective effect of a moderate, regular physical activity. Exercise delayed meal initiation and duration. FRW mice displayed food anticipatory activity compared with FR mice, which was strongly diminished with the prolongation of the protocol. The long-term nature of the protocol enabled assessment of bone parameters similar to those observed in AN patients. Both restricted groups adapted their energy metabolism differentially in the short and long term, with less fat oxidation in FRW mice and a preferential use of glucose to compensate for the chronic energy imbalance. Finally, like restrictive AN patients, FRW mice exhibited low leptin levels, high plasma concentrations of corticosterone and ghrelin, and a disruption of the estrous cycle. In conclusion, our model suggests that physical activity has beneficial effects on the adaptation to the severe condition of food restriction despite the absence of any protective effect on lean and bone mass.

  8. Asparagine deprivation mediated by Salmonella asparaginase causes suppression of activation-induced T cell metabolic reprogramming.

    PubMed

    Torres, AnnMarie; Luke, Joanna D; Kullas, Amy L; Kapilashrami, Kanishk; Botbol, Yair; Koller, Antonius; Tonge, Peter J; Chen, Emily I; Macian, Fernando; van der Velden, Adrianus W M

    2016-02-01

    Salmonellae are pathogenic bacteria that induce immunosuppression by mechanisms that remain largely unknown. Previously, we showed that a putative type II l-asparaginase produced by Salmonella Typhimurium inhibits T cell responses and mediates virulence in a murine model of infection. Here, we report that this putative L-asparaginase exhibits L-asparagine hydrolase activity required for Salmonella Typhimurium to inhibit T cells. We show that L-asparagine is a nutrient important for T cell activation and that L-asparagine deprivation, such as that mediated by the Salmonella Typhimurium L-asparaginase, causes suppression of activation-induced mammalian target of rapamycin signaling, autophagy, Myc expression, and L-lactate secretion. We also show that L-asparagine deprivation mediated by the Salmonella Typhimurium L-asparaginase causes suppression of cellular processes and pathways involved in protein synthesis, metabolism, and immune response. Our results advance knowledge of a mechanism used by Salmonella Typhimurium to inhibit T cell responses and mediate virulence, and provide new insights into the prerequisites of T cell activation. We propose a model in which l-asparagine deprivation inhibits T cell exit from quiescence by causing suppression of activation-induced metabolic reprogramming.

  9. Tumor-Specific Multiple Stimuli-Activated Dendrimeric Nanoassemblies with Metabolic Blockade Surmount Chemotherapy Resistance.

    PubMed

    Li, Yachao; Xu, Xianghui; Zhang, Xiao; Li, Yunkun; Zhang, Zhijun; Gu, Zhongwei

    2017-01-24

    Chemotherapy resistance remains a serious impediment to successful antitumor therapy around the world. However, existing chemotherapeutic approaches are difficult to cope with the notorious multidrug resistance in clinical treatment. Herein, we developed tumor-specific multiple stimuli-activated dendrimeric nanoassemblies with a metabolic blockade to completely combat both physiological barriers and cellular factors of multidrug resistance. With a sophisticated molecular and supramolecular engineering, this type of tumor-specific multiple stimuli-activated nanoassembly based on dendrimeric prodrugs can hierarchically break through the sequential physiological barriers of drug resistance, including stealthy dendritic PEGylated corona to optimize blood transportation, robust nanostructures for efficient tumor passive targeting and accumulation, enzyme-activated tumor microenvironment targeted to deepen tumor penetration and facilitate cellular uptake, cytoplasmic redox-sensitive disintegration for sufficient release of encapsulated agents, and lysosome acid-triggered nucleus delivery of antitumor drugs. In the meantime, we proposed a versatile tactic of a tumor-specific metabolism blockade for provoking several pathways (ATP restriction, apoptotic activation, and anti-apoptotic inhibition) to restrain multiple cellular factors of drug resistance. The highly efficient antitumor activity to drug-resistant MCF-7R tumor in vitro and in vivo supports this design and strongly defeats both physiological barriers and cellular factors of chemotherapy resistance. This work sets up an innovative dendrimeric nanosystem to surmount multidrug resistance, contributing to the development of a comprehensive nanoparticulate strategy for future clinical applications.

  10. Multi-cellular 3D human primary liver cell culture elevates metabolic activity under fluidic flow.

    PubMed

    Esch, Mandy B; Prot, Jean-Matthieu; Wang, Ying I; Miller, Paula; Llamas-Vidales, Jose Ricardo; Naughton, Brian A; Applegate, Dawn R; Shuler, Michael L

    2015-05-21

    We have developed a low-cost liver cell culture device that creates fluidic flow over a 3D primary liver cell culture that consists of multiple liver cell types, including hepatocytes and non-parenchymal cells (fibroblasts, stellate cells, and Kupffer cells). We tested the performance of the cell culture under fluidic flow for 14 days, finding that hepatocytes produced albumin and urea at elevated levels compared to static cultures. Hepatocytes also responded with induction of P450 (CYP1A1 and CYP3A4) enzyme activity when challenged with P450 inducers, although we did not find significant differences between static and fluidic cultures. Non-parenchymal cells were similarly responsive, producing interleukin 8 (IL-8) when challenged with 10 μM bacterial lipoprotein (LPS). To create the fluidic flow in an inexpensive manner, we used a rocking platform that tilts the cell culture devices at angles between ±12°, resulting in a periodically changing hydrostatic pressure drop between reservoirs and the accompanying periodically changing fluidic flow (average flow rate of 650 μL min(-1), and a maximum shear stress of 0.64 dyne cm(-2)). The increase in metabolic activity is consistent with the hypothesis that, similar to unidirectional fluidic flow, primary liver cell cultures increase their metabolic activity in response to fluidic flow periodically changes direction. Since fluidic flow that changes direction periodically drastically changes the behavior of other cells types that are shear sensitive, our findings support the theory that the increase in hepatic metabolic activity associated with fluidic flow is either activated by mechanisms other than shear sensing (for example increased opportunities for gas and metabolite exchange), or that it follows a shear sensing mechanism that does not depend on the direction of shear. Our mode of device operation allows us to evaluate drugs under fluidic cell culture conditions and at low device manufacturing and operation

  11. 2D-Visualization of metabolic activity with planar optical chemical sensors (optodes)

    NASA Astrophysics Data System (ADS)

    Meier, R. J.; Liebsch, G.

    2015-12-01

    Microbia plays an outstandingly important role in many hydrologic compartments, such as e.g. the benthic community in sediments, or biologically active microorganisms in the capillary fringe, in ground water, or soil. Oxygen, pH, and CO2 are key factors and indicators for microbial activity. They can be measured using optical chemical sensors. These sensors record changing fluorescence properties of specific indicator dyes. The signals can be measured in a non-contact mode, even through transparent walls, which is important for many lab-experiments. They can measure in closed (transparent) systems, without sampling or intruding into the sample. They do not consume the analytes while measuring, are fully reversible and able to measure in non-stirred solutions. These sensors can be applied as high precision fiberoptic sensors (for profiling), robust sensor spots, or as planar sensors for 2D visualization (imaging). Imaging enables to detect thousands of measurement spots at the same time and generate 2D analyte maps over a region of interest. It allows for comparing different regions within one recorded image, visualizing spatial analyte gradients, or more important to identify hot spots of metabolic activity. We present ready-to-use portable imaging systems for the analytes oxygen, pH, and CO2. They consist of a detector unit, planar sensor foils and a software for easy data recording and evaluation. Sensors foils for various analytes and measurement ranges enable visualizing metabolic activity or analyte changes in the desired range. Dynamics of metabolic activity can be detected in one shot or over long time periods. We demonstrate the potential of this analytical technique by presenting experiments on benthic disturbance-recovery dynamics in sediments and microbial degradation of organic material in the capillary fringe. We think this technique is a new tool to further understand how microbial and geochemical processes are linked in (not solely) hydrologic

  12. Evidence of active tectonics on a Roman aqueduct system (II-III century A.D.) near Rome, Italy

    NASA Astrophysics Data System (ADS)

    Marra, Fabrizio; Montone, Paola; Pirro, Mario; Boschi, Enzo

    2004-04-01

    In this paper we describe evidence of strong tectonic deformation affecting two aqueducts of Roman age (II-III century A.D.). The channels are located approximately 20 km northeast of Rome along the ancient Via Tiburtina. Brittle and ductile deformation affects these two structures, including extensional joint systems, NE-oriented faults, and horizontal distortion. This deformation is consistent with right-lateral movement on major N-striking faults, and represents the first evidence that tectonic deformation took place in historical times in the vicinity of Rome, with local strike-slip movement superimposed on a regional extensional fault system.

  13. Cytochromes P450 and species differences in xenobiotic metabolism and activation of carcinogen.

    PubMed Central

    Lewis, D F; Ioannides, C; Parke, D V

    1998-01-01

    The importance of cytochrome P450 isoforms to species differences in the metabolism of foreign compounds and activation of procarcinogens has been identified. The possible range of P450 isozymes in significant variations in toxicity exhibited by experimental rodent species may have a relevance to chemical risk assessment, especially as human P450s are likely to show changes in the way they metabolize xenobiotics. Consequently, in the safety evaluation of chemicals, we should be cautious in extrapolating results from experimental animal models to humans. This paper focuses on examples in which species differences in P450s lead to significant alterations in carcinogenic response, and includes a discussion of the current procedures for toxicity screening, with an emphasis on short-term tests. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9755138

  14. Peroxisome Proliferator-Activated Receptor Modulation during Metabolic Diseases and Cancers: Master and Minions

    PubMed Central

    Nigro, Angela; La Rosa, Valentina Lucia; Rossetti, Paola; Rapisarda, Agnese Maria Chiara; Condorelli, Rosita Angela; Corrado, Francesco; Buscema, Massimo

    2016-01-01

    The prevalence of obesity and metabolic diseases (such as type 2 diabetes mellitus, dyslipidaemia, and cardiovascular diseases) has increased in the last decade, in both industrialized and developing countries. This also coincided with our observation of a similar increase in the prevalence of cancers. The aetiology of these diseases is very complex and involves genetic, nutritional, and environmental factors. Much evidence indicates the central role undertaken by peroxisome proliferator-activated receptors (PPARs) in the development of these disorders. Due to the fact that their ligands could become crucial in future target-therapies, PPARs have therefore become the focal point of much research. Based on this evidence, this narrative review was written with the purpose of outlining the effects of PPARs, their actions, and their prospective uses in metabolic diseases and cancers. PMID:28115924

  15. Involvement of electron and hydrogen transfers through redox metabolism on activity and toxicity of the nimesulide.

    PubMed

    Borges, Rosivaldo S; Oliveira, Juliana P; Matos, Rafaelle F; Chaves Neto, Antonio M J; Carneiro, Agnaldo S; Monteiro, Marta C

    2015-07-01

    An electronic study of nimesulide was performed by using density functional theory calculations. The activities of the six different derivatives were related with electron donating or accepting capacities. All compounds which had nitro moiety had low electron donating and high electron accepting capacities. However, the reduced derivative of nimesulide have more electron donating capacity than other compounds. The highest spin density contribution in nitro and lowest spin density contribution on phenoxyl moieties can be related with preferential metabolism by reduction when compared with the oxidation. The redox behavior between nitro and amino groups can be related with anti-inflammatory mechanism of nimesulide. These results explain the redox influence of nitro moiety on biological metabolism and mechanism of nimesulide.

  16. Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response.

    PubMed

    Moreau, Amélie; Vilarem, Marie José; Maurel, Patrick; Pascussi, Jean Marc

    2008-01-01

    Xenobiotic and drug metabolism and transport are managed by a large number of genes coordinately regulated by at least three nuclear receptors or xenosensors: aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR, NR1I3), and pregnane X receptor (PXR, NR1I2). Initially characterized as xenosensors, it is now evident that CAR and PXR also trigger pleiotropic effects on liver function. Recent studies have shown the existence of crosstalk between xenosensors and other nuclear receptors or transcription factors controlling endogenous signaling pathways which regulate physiological functions. This review is focused on recent observations showing that activation of CAR and PXR alters lipid metabolism, glucose homeostasis, and inflammation by interfering with HNF4alpha, FoxO1, FoxA2, PGC1alpha, or NFkB p65. Such crosstalks explain clinical observations and provide molecular mechanisms allowing understanding how xenobiotics and drugs may affect physiological functions and provoke endocrine disruptions.

  17. Activation of phosphatidic acid metabolism of human erythrocyte membranes by perfringolysin O

    SciTech Connect

    Saito, M.; Ando, S.; Mitsui, K.; Homma, Y.; Takenawa, T.

    1986-05-29

    The effect of perfringolysin O on the lipid metabolism of human erythrocyte membranes was investigated. Erythrocytes were prelabeled with (/sup 3/H)arachidonic acid and (/sup 32/P)inorganic phosphate. In the presence of calcium ion (5.5 mM), the effect of perfringolysin O on lipid metabolism was very similar to that of an calcium-ionophore A23187. In the absence of calcium ion, the accumulation of phosphatidic acid and its following decreasing trend were observed during the reaction with the toxin. Such changes were not caused by filipin. These results suggest that perfringolysin O causes the activation of a diglyceride-phosphatidic acid cycle, which might be involved in the calcium transport.

  18. Mitochondrial superoxide flashes: metabolic biomarkers of skeletal muscle activity and disease

    PubMed Central

    Wei, Lan; Salahura, Gheorghe; Boncompagni, Simona; Kasischke, Karl A.; Protasi, Feliciano; Sheu, Shey-Shing; Dirksen, Robert T.

    2011-01-01

    Mitochondrial superoxide flashes (mSOFs) are stochastic events of quantal mitochondrial superoxide generation. Here, we used flexor digitorum brevis muscle fibers from transgenic mice with muscle-specific expression of a novel mitochondrial-targeted superoxide biosensor (mt-cpYFP) to characterize mSOF activity in skeletal muscle at rest, following intense activity, and under pathological conditions. Results demonstrate that mSOF activity in muscle depended on electron transport chain and adenine nucleotide translocase functionality, but it was independent of cyclophilin-D-mediated mitochondrial permeability transition pore activity. The diverse spatial dimensions of individual mSOF events were found to reflect a complex underlying morphology of the mitochondrial network, as examined by electron microscopy. Muscle activity regulated mSOF activity in a biphasic manner. Specifically, mSOF frequency was significantly increased following brief tetanic stimulation (18.1±1.6 to 22.3±2.0 flashes/1000 μm2·100 s before and after 5 tetani) and markedly decreased (to 7.7±1.6 flashes/1000 μm2·100 s) following prolonged tetanic stimulation (40 tetani). A significant temperature-dependent increase in mSOF frequency (11.9±0.8 and 19.8±2.6 flashes/1000 μm2·100 s at 23°C and 37°C) was observed in fibers from RYR1Y522S/WT mice, a mouse model of malignant hyperthermia and heat-induced hypermetabolism. Together, these results demonstrate that mSOF activity is a highly sensitive biomarker of mitochondrial respiration and the cellular metabolic state of muscle during physiological activity and pathological oxidative stress.—Wei, L., Salahura, G., Boncompagni, S., Kasischke, K. A., Protasi, F., Sheu, S.-S., Dirksen, R. T. Mitochondrial superoxide flashes: metabolic biomarkers of skeletal muscle activity and disease. PMID:21646399

  19. Oxygen Affects Gut Bacterial Colonization and Metabolic Activities in a Gnotobiotic Cockroach Model

    PubMed Central

    Tegtmeier, Dorothee; Thompson, Claire L.; Schauer, Christine

    2015-01-01

    The gut microbiota of termites and cockroaches represents complex metabolic networks of many diverse microbial populations. The distinct microenvironmental conditions within the gut and possible interactions among the microorganisms make it essential to investigate how far the metabolic properties of pure cultures reflect their activities in their natural environment. We established the cockroach Shelfordella lateralis as a gnotobiotic model and inoculated germfree nymphs with two bacterial strains isolated from the guts of conventional cockroaches. Fluorescence microscopy revealed that both strains specifically colonized the germfree hindgut. In diassociated cockroaches, the facultatively anaerobic strain EbSL (a new species of Enterobacteriaceae) always outnumbered the obligately anaerobic strain FuSL (a close relative of Fusobacterium varium), irrespective of the sequence of inoculation, which showed that precolonization by facultatively anaerobic bacteria does not necessarily favor colonization by obligate anaerobes. Comparison of the fermentation products of the cultures formed in vitro with those accumulated in situ indicated that the gut environment strongly affected the metabolic activities of both strains. The pure cultures formed the typical products of mixed-acid or butyrate fermentation, whereas the guts of gnotobiotic cockroaches accumulated mostly lactate and acetate. Similar shifts toward more-oxidized products were observed when the pure cultures were exposed to oxygen, which corroborated the strong effects of oxygen on the metabolic fluxes previously observed in termite guts. Oxygen microsensor profiles of the guts of germfree, gnotobiotic, and conventional cockroaches indicated that both gut tissue and microbiota contribute to oxygen consumption and suggest that the oxygen status influences the colonization success. PMID:26637604

  20. Oxygen Affects Gut Bacterial Colonization and Metabolic Activities in a Gnotobiotic Cockroach Model.

    PubMed

    Tegtmeier, Dorothee; Thompson, Claire L; Schauer, Christine; Brune, Andreas

    2015-12-04

    The gut microbiota of termites and cockroaches represents complex metabolic networks of many diverse microbial populations. The distinct microenvironmental conditions within the gut and possible interactions among the microorganisms make it essential to investigate how far the metabolic properties of pure cultures reflect their activities in their natural environment. We established the cockroach Shelfordella lateralis as a gnotobiotic model and inoculated germfree nymphs with two bacterial strains isolated from the guts of conventional cockroaches. Fluorescence microscopy revealed that both strains specifically colonized the germfree hindgut. In diassociated cockroaches, the facultatively anaerobic strain EbSL (a new species of Enterobacteriaceae) always outnumbered the obligately anaerobic strain FuSL (a close relative of Fusobacterium varium), irrespective of the sequence of inoculation, which showed that precolonization by facultatively anaerobic bacteria does not necessarily favor colonization by obligate anaerobes. Comparison of the fermentation products of the cultures formed in vitro with those accumulated in situ indicated that the gut environment strongly affected the metabolic activities of both strains. The pure cultures formed the typical products of mixed-acid or butyrate fermentation, whereas the guts of gnotobiotic cockroaches accumulated mostly lactate and acetate. Similar shifts toward more-oxidized products were observed when the pure cultures were exposed to oxygen, which corroborated the strong effects of oxygen on the metabolic fluxes previously observed in termite guts. Oxygen microsensor profiles of the guts of germfree, gnotobiotic, and conventional cockroaches indicated that both gut tissue and microbiota contribute to oxygen consumption and suggest that the oxygen status influences the colonization success.

  1. Combined therapeutic use of AdGFPFasL and small molecule inhibitors of ceramide metabolism in prostate and head and neck cancers: a status report.

    PubMed

    Norris, J S; Bielawska, A; Day, T; El-Zawahri, A; ElOjeimy, S; Hannun, Y; Holman, D; Hyer, M; Landon, C; Lowe, S; Dong, J Y; McKillop, J; Norris, K; Obeid, L; Rubinchik, S; Tavassoli, M; Tomlinson, S; Voelkel-Johnson, C; Liu, X

    2006-12-01

    As of January 2005, there were 1020 gene therapy clinical trials ongoing worldwide with 675 or 66.2% devoted to cancer gene therapy. The majority are occurring in the US and Europe (http://www.wiley.co.uk/genetherapy/clinical/). At the present time, to our knowledge there are no trials that employ gene delivery of Fas Ligand (FasL). As an important note, and in contrast to somatic cell therapy trials, there are no reported deaths due to therapeutic vector administration in any cancer gene therapy trial. That said, from our studies and from the published literature, the issue of gene delivery remains the major obstacle to successfully employing gene therapy for cancer treatment. Numerous laboratories are studying this with many different approaches. My co-workers and I have focused on the delivery issue by using various approaches that address tumor targeting and transgene expression. In addition, we are focusing on enhancing tumor cell killing via the bystander effect and through use of small molecules to enhance bystander activity.

  2. Acetate metabolism does not reflect astrocytic activity, contributes directly to GABA synthesis, and is increased by silent information regulator 1 activation.

    PubMed

    Rowlands, Benjamin D; Klugmann, Matthias; Rae, Caroline D

    2017-03-01

    [(13) C]Acetate is known to label metabolites preferentially in astrocytes rather than neurons and it has consequently been used as a marker for astrocytic activity. Recent discoveries suggest that control of acetate metabolism and its contributions to the synthesis of metabolites in brain is not as simple as first thought. Here, using a Guinea pig brain cortical tissue slice model metabolizing [1-(13) C]D-glucose and [1,2-(13) C]acetate, we investigated control of acetate metabolism and the degree to which it reflects astrocytic activity. Using a range of [1,2-(13) C]acetate concentrations, we found that acetate is a poor substrate for metabolism and will inhibit metabolism of itself and of glucose at concentrations in excess of 2 mmol/L. By activating astrocytes using potassium depolarization, we found that use of [1,2-(13) C]acetate to synthesize glutamine decreases significantly under these conditions showing that acetate metabolism does not necessarily reflect astrocytic activity. By blocking synthesis of glutamine using methionine sulfoximine, we found that significant amount of [1,2-(13) C]acetate are still incorporated into GABA and its metabolic precursors in neurons, with around 30% of the GABA synthesized from [1,2-(13) C]acetate likely to be made directly in neurons rather than from glutamine supplied by astrocytes. Finally, to test whether activity of the acetate metabolizing enzyme acetyl-CoA synthetase is under acetylation control in the brain, we incubated slices with the AceCS1 deacetylase silent information regulator 1 (SIRT1) activator SRT 1720 and showed consequential increased incorporation of [1,2-(13) C]acetate into metabolites. Taken together, these data show that acetate metabolism is not directly nor exclusively related to astrocytic metabolic activity, that use of acetate is related to enzyme acetylation and that acetate is directly metabolized to a significant degree in GABAergic neurons. Changes in acetate metabolism should be

  3. The Relationship Between Physical Activity and the Metabolic Syndrome Score in Children

    PubMed Central

    McKune, Andrew J.; Brophy, Patricia; Geyer, Gabriel; Hickner, Robert C.

    2015-01-01

    The relationship between physical activity levels and the metabolic syndrome (MetSyn) score was examined in 72 boys and girls (9.5 ± 1.2 years). A fasting blood draw was obtained; waist circumference and blood pressure measured, and an accelerometer was worn for 5 days. Established cut points were used to estimate time spent in moderate, vigorous, moderate-to-vigorous (MVPA), and total physical activity. A continuous MetSyn score was created from blood pressure, waist circumference, high-density-lipoprotein, triglyceride, and glucose values. Regression analysis was used to examine the relationship between physical activity levels, the MetSyn score, and its related components. Logistic regression was used to examine the association between meeting physical activity recommendations, the MetSyn score, and its related components. All analyses were controlled for body mass index group, age, sex, and race. Time spent in different physical activity levels or meeting physical activity recommendations (OR: 0.87, 95%CI: 0.69-1.09) was not related with the MetSyn score after controlling for potential confounders (p>0.05). Moderate physical activity, MVPA, and meeting physical activity recommendations were related to a lower diastolic blood pressure (p<0.05). No other relationships were observed (p>0.05). While physical activity participation was not related with the MetSyn, lower diastolic blood pressure values were related to higher physical activity levels. PMID:25902555

  4. Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice

    PubMed Central

    Russo, Matias; Fabersani, Emanuel; Abeijón-Mukdsi, María C.; Ross, Romina; Fontana, Cecilia; Benítez-Páez, Alfonso; Gauffin-Cano, Paola; Medina, Roxana B.

    2016-01-01

    The purpose of this study was to determine whether the administration of the feruloyl esterase (FE)-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR) mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group), CR diet Group (CR Group) and CR diet plus L. fermentum Group (CR-Lf Group). CR diet was administered during 45 days and CRL1446 strain was given in the dose of 108 cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS) levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020) than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025), total cholesterol (p = 0.005) and glucose (p < 0.0001) levels) and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006)) parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions. PMID:27399766

  5. Regulation of bacterial metabolic activity by dissolved organic carbon and viruses

    NASA Astrophysics Data System (ADS)

    Xu, Jie; Jing, Hongmei; Sun, Mingming; Harrison, Paul J.; Liu, Hongbin

    2013-12-01

    regulation of bacterial metabolic activity by viruses and dissolved organic carbon (DOC) was examined using natural microbial communities in three treatments (active viruses, inactive viruses, and virus free) at two contrasting coastal sites (pristine vs. eutrophic) with substantial differences in environmental conditions during the wet and dry seasons. Our results showed that net growth rates and production of bacterioplankton were reduced primarily by viruses via repressing metabolically active bacteria with high nucleic acid (HNA) content which had a high capacity for incorporating carbon, while bacterial respiration was primarily regulated by DOC lability. The quality of organic matter played a more important role in regulating bacterial growth efficiency (BGE) than the supply of organic matter in eutrophic coastal waters. The lack of HMW-DOC and high carbon demand in the virus-free treatment resulted in a significant increase in cell-specific bacterial respiration, which was responsible for the lowest bacterial growth efficiency among the three treatments. The presence of viruses did not necessarily lower bacterial growth efficiency since virus-induced mortality alleviated bacterial carbon demand and enhanced carbon cycling. Virus-induced mortality was greater in relatively pristine waters than eutrophic waters, likely since the high supply of substrates alleviated the pressure of viral infection, through extracellular proteases produced by bacteria, which might result in the hydrolytic destruction or modification of viral capsids. An important implication of our results was that the input of riverine DOC and nutrients improved bacterial metabolic activity by alleviating virus-induced mortality of bacteria in estuarine and coastal waters.

  6. Metabolism of Benzyladenine is Impaired in a Mutant of Arabidopsis thaliana Lacking Adenine Phosphoribosyltransferase Activity 1

    PubMed Central

    Moffatt, Barbara; Pethe, Claude; Laloue, Michel

    1991-01-01

    Formation of the riboside-5′-monophosphate is a general feature of the metabolism of cytokinins in plants. As part of a study of the biological significance of the nucleotide form of cytokinins, we analyzed a mutant of Arabidopsis thaliana deficient in adenine phosphoribosyltransferase (APRT) activity for its ability to metabolize N6-benzyladenine (BA). Formation of N6-benzyladenosine-5′-monophosphate (BAMP) was assayed in vivo, by feeding tritiated BA to wild-type and mutant plantlets, and in crude plantlet extracts. Metabolites were separated by high performance liquid chromatography and quantitated by on-line liquid scintillation spectrometry. BA was rapidly absorbed by A. thaliana plantlets and primarily converted to BAMP and to BA 7- and 9-glucosides. BA was also rapidly absorbed by APRT-deficient plantlets, but its conversion to BAMP was strongly reduced. Formation of BAMP from N6-benzyladenosine was not affected in the mutant plantlets. In vitro conversion of BA to its nucleoside-5′-monophosphate was detected in crude extracts of wild-type plantlets, but not in extracts of APRT-deficient plantlets. Therefore, results of both assays indicate that APRT-deficient tissue does not convert BA to BAMP to a significant extent. Further, nondenaturing isoelectric focusing analysis of APRT activity in leaf extracts indicated that the enzyme activities which metabolize adenine and BA into their corresponding riboside-5′-monophosphate in extracts of wild-type plantlets have the same apparent isoelectric point. These activities were not detected in extracts prepared from APRT-deficient plantlets. Thus, these results demonstrate that APRT is the main enzyme which converts BA to its nucleotide form in young A. thaliana plants and that the ribophosphorylation of BA is not a prerequisite of its absorption by the plantlets. Images Figure 4 PMID:16668070

  7. ADS Based on Linear Accelerators

    NASA Astrophysics Data System (ADS)

    Pan, Weimin; Dai, Jianping

    An accelerator-driven system (ADS), which combines a particle accelerator with a subcritical core, is commonly regarded as a promising device for the transmutation of nuclear waste, as well as a potential scheme for thorium-based energy production. So far the predominant choice of the accelerator for ADS is a superconducting linear accelerator (linac). This article gives a brief overview of ADS based on linacs, including the motivation, principle, challenges and research activities around the world. The status and future plan of the Chinease ADS (C-ADS) project will be highlighted and discussed in depth as an example.

  8. Modulation of fructokinase activity of potato (Solanum tuberosum) results in substantial shifts in tuber metabolism.

    PubMed

    Davies, Howard V; Shepherd, Louise V T; Burrell, Michael M; Carrari, Fernando; Urbanczyk-Wochniak, Ewa; Leisse, Andrea; Hancock, Robert D; Taylor, Mark; Viola, Roberto; Ross, Heather; McRae, Diane; Willmitzer, Lothar; Fernie, Alisdair R

    2005-07-01

    Potato plants (Solanum tuberosum L. cvs Desiree and Record) transformed with sense and antisense constructs of a cDNA encoding the potato fructokinase StFK1 exhibited altered transcription of this gene, altered amount of protein and altered enzyme activities. Measurement of the maximal catalytic activity of fructokinase revealed a 2-fold variation in leaf (from 90 to 180% of wild type activity) and either a 10- or 30-fold variation in tuber (from 10 or 30% to 300% in Record and Desiree, respectively) activity. The comparative effect of the antisense construct in leaf and tuber tissue suggests that this isoform is only a minor contributor to the total fructokinase activity in the leaf but the predominant isoform in the tuber. Antisense inhibition of the fructokinase resulted in a reduced tuber yield; however, its overexpression had no impact on this parameter. The modulation of fructokinase activity had few, consistent effects on carbohydrate levels, with the exception of a general increase in glucose content in the antisense lines, suggesting that this enzyme is not important for the control of starch synthesis. However, when metabolic fluxes were estimated, it became apparent that the transgenic lines display a marked shift in metabolism, with the rate of redistribution of radiolabel to sucrose markedly affected by the activity of fructokinase. These data suggest an important role for fructokinase, acting in concert with sucrose synthase, in maintaining a balance between sucrose synthesis and degradation by a mechanism independent of that controlled by the hexose phosphate-mediated activation of sucrose phosphate synthase.

  9. Understanding the structure-function relationship between FGF19 and its mitogenic and metabolic activities.

    PubMed

    Wu, Xinle; Li, Yang

    2012-01-01

    FGF19 differs from the classical FGFs in that it has a much-reduced heparan sulfate proteoglycan binding affinity that allows it to act as endocrine hormone. Although FGF19 regulates several different metabolic activities, it still activates downstream signaling pathways through FGF receptors, in a similar manner to that seen in classical FGFs. Aberrant FGF signaling has been implicated in tumor development, and mouse models have confirmed that FGF19 has the potential to induce hepatocellular carcinoma. Treatment with anti-FGF19 antibody suppressed tumor progression in both FGF19 transgenic mice and colon cancer cell xenograft models. FGFR4, the predominant FGF receptor expressed in the liver, may play an important role in FGF19-mediated tumorigenesis. This review reports the current advances in understanding the structure-function relationship between FGF19 and its interactions with FGFRs, its physiological activities, and its differences from FGF21. The review also discusses strategies to separate the mitogenic and metabolic activities for the development of potential therapeutic molecules based on FGF19.

  10. Metabolic activity of moulds as a factor of building materials biodegradation.

    PubMed

    Gutarowska, Beata

    2010-01-01

    This paper presents the effect of building materials on the growth and metabolic activity of moulds. In cultures of Aspergillus and Penicillium moulds grown on a model medium with the addition of building materials, the biomass of mycelium, its cellular components--glucan, chitin, ergosterol and the spectrum of enzymes and organic acids produced in the medium were investigated. It was found that on the medium with wallpaper moulds produced more biomass and extracellular enzymes, mainly glycolytic ones. On medium with mortar the growth of mycelium was impeded, production of biomass was 60% smaller, the quantity of chitin, glucan and ergosterol decreased 13-41%, and the activity of most enzymes was reduced; however the moulds intensively produced organic acids: malic, succinic and oxalic acid. The largest acid production activity was found in medium with addition of mortar; moulds produced the greatest variety of acids and in greater quantities than in the control medium. Metabolic activity of the moulds depends on the type of building material, and may lead to biodeterioration of these materials.

  11. Tunable regulation of CREB DNA binding activity couples genotoxic stress response and metabolism

    PubMed Central

    Kim, Sang Hwa; Trinh, Anthony T.; Larsen, Michele Campaigne; Mastrocola, Adam S.; Jefcoate, Colin R.; Bushel, Pierre R.; Tibbetts, Randal S.

    2016-01-01

    cAMP response element binding protein (CREB) is a key regulator of glucose metabolism and synaptic plasticity that is canonically regulated through recruitment of transcriptional coactivators. Here we show that phosphorylation of CREB on a conserved cluster of Ser residues (the ATM/CK cluster) by the DNA damage-activated protein kinase ataxia-telangiectasia-mutated (ATM) and casein kinase1 (CK1) and casein kinase2 (CK2) positively and negatively regulates CREB-mediated transcription in a signal dependent manner. In response to genotoxic stress, phosphorylation of the ATM/CK cluster inhibited CREB-mediated gene expression, DNA binding activity and chromatin occupancy proportional to the number of modified Ser residues. Paradoxically, substoichiometric, ATM-independent, phosphorylation of the ATM/CK cluster potentiated bursts in CREB-mediated transcription by promoting recruitment of the CREB coactivator, cAMP-regulated transcriptional coactivators (CRTC2). Livers from mice expressing a non-phosphorylatable CREB allele failed to attenuate gluconeogenic genes in response to DNA damage or fully activate the same genes in response to glucagon. We propose that phosphorylation-dependent regulation of DNA binding activity evolved as a tunable mechanism to control CREB transcriptional output and promote metabolic homeostasis in response to rapidly changing environmental conditions. PMID:27431323

  12. The African hedgehog (Atelerix albiventris): Low phase I and phase II metabolism activities.

    PubMed

    Saengtienchai, Aksorn; Ikenaka, Yoshinori; Bortey-Sam, Nesta; Jermnark, Usuma; Mizukawa, Hazuki; Kawai, Yusuke K; Nakayama, Shouta M M; Ishizuka, Mayumi

    2016-12-01

    The African hedgehog, Atelerix albiventris, is a spiny mammal that has become popular as an exotic pet in many countries. To elucidate the ability of hedgehogs to metabolize xenobiotics, the animals were exposed to polycyclic aromatic hydrocarbon, pyrene. The in vivo exposure study indicated that pyrene was biotransformed to glucuronide and sulfate conjugates, such as pyrene-1-glucuronide, pyrene-1-sulfate, and pyrenediol-sulfate, and excreted in the urine. Pyrene-1-glucuronide was the main metabolite, and limited sulfate conjugate excretion was observed. The main products excreted in feces were 1-hydroxypyrene and pyrene. Based on the results of the in vivo exposure study, in vitro enzymatic kinetic experiments were performed using various substrates and compared to rats and pigs. The enzyme efficiencies of cytochrome P450 (CYP)-mediated ethoxyresorufin O-deethylase activity and warfarin 4'-, 6-, and 8-hydroxylation activity in hedgehogs were lower than those of rats. Furthermore, UDP-glucuronosyltransferase activity in hedgehogs also had a lower Km value than that in pigs. Interestingly, the enzyme efficiencies of sulfation activity toward 1-hydroxypyrene and β-estradiol in hedgehogs were significantly lower than those in pigs. These observations suggested that phenol and estrogen sulfotransferases may have limited roles in xenobiotic metabolism in hedgehogs.

  13. Metabolic syndrome, platelet activation and the development of transient ischemic attack or thromboembolic stroke.

    PubMed

    van Rooy, Mia-Jeanne; Pretorius, Etheresia

    2015-03-01

    Stroke is the second most common cause of mortality in the world today, where transient ischemic attack (TIA) is a period of focal ischemia, the symptoms of which resemble a thromboembolic stroke. Contrary to stroke, TIA symptoms typically last less than one hour and necrosis is absent. Stroke is often preceded by TIA, making it an important predictor of future ischemic events. The causal role of atherosclerosis in the development of TIA is well established, however, research indicates that the atherosclerotic process begins years earlier with the development of metabolic syndrome, which affects approximately 45% of the adult population worldwide. Metabolic syndrome is present if three or more of the following is present: increased waist circumference, increased triglycerides, decreased HDL, increased fasting glucose and hypertension. This syndrome causes systemic inflammation that activates the coagulation system and may cause the formation of pathological thrombi. The role of platelets in stroke has been studied and platelet activation pathways identified. ADP and thromboxane A(2) are the most common activators of platelets in normal physiology. Several pharmacological treatments have been employed to prevent the activation of platelets, the most common of which include aspirin and P2Y(12)-inhibitors. Although treatment is administered strokes and subsequent TIAs are very common in individuals that suffered an initial event. This indicates that research needs to be done in order to elucidate new therapeutic targets, but also to better treat ischemic events to not only decrease the amount of recurring events but also decrease stroke mortality worldwide.

  14. Metabolomics reveals a novel vitamin E metabolite and attenuated vitamin E metabolism upon PXR activation.

    PubMed

    Cho, Joo-Youn; Kang, Dong Wook; Ma, Xiaochao; Ahn, Sung-Hoon; Krausz, Kristopher W; Luecke, Hans; Idle, Jeffrey R; Gonzalez, Frank J

    2009-05-01

    Pregnane X receptor (PXR) is an important nuclear receptor xenosensor that regulates the expression of metabolic enzymes and transporters involved in the metabolism of xenobiotics and endobiotics. In this study, ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS), revealed altered urinary metabolomes in both Pxr-null and wild-type mice treated with the mouse PXR activator pregnenolone 16alpha-carbonitrile (PCN). Multivariate data analysis revealed that PCN significantly attenuated the urinary vitamin E metabolite alpha-carboxyethyl hydroxychroman (CEHC) glucuronide together with a novel metabolite in wild-type but not Pxr-null mice. Deconjugation experiments with beta-glucuronidase and beta-glucosidase suggested that the novel urinary metabolite was gamma-CEHC beta-D-glucoside (Glc). The identity of gamma-CEHC Glc was confirmed by chemical synthesis and by comparing tandem mass fragmentation of the urinary metabolite with the authentic standard. The lower urinary CEHC was likely due to PXR-mediated repression of hepatic sterol carrier protein 2 involved in peroxisomal beta-oxidation of branched-chain fatty acids (BCFA). Using a combination of metabolomic analysis and a genetically modified mouse model, this study revealed that activation of PXR results in attenuated levels of the two vitamin E conjugates, and identification of a novel vitamin E metabolite, gamma-CEHC Glc. Activation of PXR results in attenuated levels of the two vitamin E conjugates that may be useful as biomarkers of PXR activation.

  15. Orientifolded locally AdS3 geometries

    NASA Astrophysics Data System (ADS)

    Loran, F.; Sheikh-Jabbari, M. M.

    2011-01-01

    Continuing the analysis of [Loran F and Sheikh-Jabbari M M 2010 Phys. Lett. B 693 184-7], we classify all locally AdS3 stationary axi-symmetric unorientable solutions to AdS3 Einstein gravity and show that they are obtained by applying certain orientifold projection on AdS3, BTZ or AdS3 self-dual orbifold, respectively, O-AdS3, O-BTZ and O-SDO geometries. Depending on the orientifold fixed surface, the O-surface, which is either a space-like 2D plane or a cylinder, or a light-like 2D plane or a cylinder, one can distinguish four distinct cases. For the space-like orientifold plane or cylinder cases, these geometries solve AdS3 Einstein equations and are hence locally AdS3 everywhere except at the O-surface, where there is a delta-function source. For the light-like cases, the geometry is a solution to Einstein equations even at the O-surface. We discuss the causal structure for static, extremal and general rotating O-BTZ and O-SDO cases as well as the geodesic motion on these geometries. We also discuss orientifolding Poincaré patch AdS3 and AdS2 geometries as a way to geodesic completion of these spaces and comment on the 2D CFT dual to the O-geometries.

  16. Recommended Levels of Physical Activity Are Associated with Reduced Risk of the Metabolic Syndrome in Mexican-Americans

    PubMed Central

    Wu, Shenghui; Fisher-Hoch, Susan P.; Reininger, Belinda; McCormick, Joseph B.

    2016-01-01

    Purpose To measure the association between physical activity and the metabolic syndrome risk in Mexican-Americans. Methods Participants were drawn from the Cameron County Hispanic Cohort (n = 3,414), a randomly selected Mexican-American cohort in Texas on the US-Mexico border. Moderate and vigorous physical activity was assessed using reliable and validated instruments. The metabolic syndrome was defined as having 3 or more metabolic abnormalities. Results One thousand five hundred and twenty-four participants of the cohort (45.02%) were found to have the metabolic syndrome. Compared to participants who did not meet US physical activity guidelines, participants who met physical activity guidelines of 150 moderate and vigorous minutes per week (≥ 600 MET adjusted minutes) had 36% lower risk for the metabolic syndrome (OR = 0.64; 95% CI: 0.42–0.98), and participants with total minutes per week of moderate and vigorous/strenuous activity greater than 743 MET adjusted minutes had 37% lower risk for the metabolic syndrome (OR = 0.63; 95% CI: 0.42–0.94) compared with their counterparts, after adjusting for age, gender, annual household income, body mass index, smoking and alcohol drinking status, total portions of fruit and vegetable intake, census tracts and blocks, and survey version for physical activity. Conclusions Meeting or exceeding physical activity guidelines significantly was inversely associated with the risk for the metabolic syndrome in Mexican-Americans. Improving levels of physical activity appears to be an effective target for the metabolic syndrome prevention and control among Mexican-Americans independent of other factors. PMID:27054324

  17. Metabolic activation of herbal and dietary constituents and its clinical and toxicological implications: an update.

    PubMed

    Zhou, Shu-Feng; Xue, Charlie Changli; Yu, Xue-Qing; Wang, Guangji

    2007-08-01

    In recent years, there has been a globally increasing application of herbal medicines and dietary supplements to treat various chronic diseases and to promote health. However, there are increasing clinical reports on the organ toxicities associated with consumption of herbal medicines. This review updates the knowledge on metabolic activation of herbal components and its clinical and toxicological implications. Like many synthetic drugs undergoing metabolic activation to form reactive metabolites which are often associated with drug toxicity, it is recognized that some herbal components may also be converted to toxic, or even mutagenetic and carcinogenic metabolites by cytochrome P450s (CYPs) and less frequently by Phase II conjugating enzymes. This is exemplified by aristolochic acids (AAs) in Aristolochia spp, which undergo reduction of the nitro group by hepatic CYP1A1/2 or peroxidases in extrahepatic tissues to generate highly reactive cyclic nitrenium ions. The latter can react with macromolecules (DNA and protein), resulting in activation of H-ras oncogene and gene mutation in renal cells and finally carcinogenesis of the kidneys. Some naturally occurring flavonoids (e.g. quercetin) and alkenylbenzenes (e.g. safrole, methyleugenol and estragole) can undergo metabolic activation by sequential 1-hydroxylation and sulfation, resulting in reactive intermediates capable of forming DNA adducts and finally genotoxicity. Additional examples are pulegone present in essential oils from many mint species; and teucrin A, a diterpenoid found in germander (Teuchrium chamaedrys) used as an adjuvant to slimming dietary supplements but caused severe hepatotoxicity. Extensive pulegone metabolism generated p-cresol that was a glutathione depletory, whereas the furan ring of the diterpenoids in germander was oxidized by CYP3A4 to reactive epoxide which can inactivate hepatic CYP3A and epoxide hydrolase through covalent binding. The hepatotoxic and carcinogenic species of plant

  18. Immunosuppressive activity enhances central carbon metabolism and bioenergetics in myeloid-derived suppressor cells in vitro models

    PubMed Central

    2012-01-01

    Background The tumor microenvironment contains a vast array of pro- and anti-inflammatory cytokines that alter myelopoiesis and lead to the maturation of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs). Incubating bone marrow (BM) precursors with a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) generated a tumor-infiltrating MDSC-like population that impaired anti-tumor specific T-cell functions. This in vitro experimental approach was used to simulate MDSC maturation, and the cellular metabolic response was then monitored. A complementary experimental model that inhibited L-arginine (L-Arg) metabolizing enzymes in MSC-1 cells, an immortalized cell line derived from primary MDSCs, was used to study the metabolic events related to immunosuppression. Results Exposure of BM cells to GM-CSF and IL-6 activated, within 24 h, L-Arg metabolizing enzymes which are responsible for the MDSCs immunosuppressive potential. This was accompanied by an increased uptake of L-glutamine (L-Gln) and glucose, the latter being metabolized by anaerobic glycolysis. The up-regulation of nutrient uptake lead to the accumulation of TCA cycle intermediates and lactate as well as the endogenous synthesis of L-Arg and the production of energy-rich nucleotides. Moreover, inhibition of L-Arg metabolism in MSC-1 cells down-regulated central carbon metabolism activity, including glycolysis, glutaminolysis and TCA cycle activity, and led to a deterioration of cell bioenergetic status. The simultaneous increase of cell specific concentrations of ATP and a decrease in ATP-to-ADP ratio in BM-derived MDSCs suggested cells were metabolically active during maturation. Moreover, AMP-activated protein kinase (AMPK) was activated during MDSC maturation in GM-CSF and IL-6–treated cultures, as revealed by the continuous increase of AMP-to-ATP ratios and the phosphorylation of AMPK. Likewise, AMPK activity was decreased in MSC-1

  19. Metabolic activity of sodium, measured by neutron activation, in the hands of patients suffering from bone diseases: concise communication

    SciTech Connect

    Spinks, T.J.; Bewley, D.K.; Paolillo, M.; Vlotides, J.; Joplin, G.F.; Ranicar, A.S.O.

    1980-01-01

    Turnover of sodium in the human hand was studied by neutron activation. Patients suffering from various metabolic abnormalities affecting the skeleton, who were undergoing routine neutron activation for the measurement of calcium, were investigated along with a group of healthy volunteers. Neutron activation labels the sodium atoms simultaneously and with equal probability regardless of the turnover time of individual body compartments. The loss of sodium can be described either by a sum of two exponentials or by a single power function. Distinctions between patients and normal subjects were not apparent from the exponential model but were brought out by the power function. The exponent of time in the latter is a measure of clearance rate. The mean values of this parameter in (a) a group of patients suffering from acromegaly; (b) a group including Paget's disease, osteoporosis, Cushing's disease, and hyperparathyroidism; and (c) a group of healthy subjects, were found to be significantly different from each other.

  20. Effects of twelve months ethanol feeding on rat liver metabolic activity.

    PubMed

    Biewald, J; Bromme, H J; Nilius, R; Langner, J

    1999-03-01

    Thirty male Wistar rats were fed with 15% ethanol (V/V) for one year. Thirty other male animals were the control group. To determine the possible metabolic disturbances caused by chronic ethanol feeding in blood we measured in blood metabolic parameters, and in a liver perfusion assay the hepatic insulin clearance and hepatic urea production in these animals. Between the ethanol-fed and the control animals there were significant differences in the following parameters: blood insulin concentration (47 vs. 2 microU/ml) and activities of amino acid transferases in liver homogenates at the end of the perfusion experiments (ASAT, 5950 vs. 70; ALAT, 3632 vs. 93 U/l). The other parameters were still normal in the ethanol-fed animals. Thus in these experiments after 12 months of 15% (V/V) ethanol feeding the rats still showed only a state of beginning metabolic disturbances in the liver. The results are discussed under consideration of the formation of acetaldehyde protein adducts in all rat organs investigated, namely, liver, kidney, heart and skeleton muscle, gut and spleen.

  1. Geographic differences in digoxin inactivation, a metabolic activity of the human anaerobic gut flora.

    PubMed Central

    Mathan, V I; Wiederman, J; Dobkin, J F; Lindenbaum, J

    1989-01-01

    The inactivation of digoxin by conversion to reduced metabolites (digoxin reduction products, or DRP), a function of the anaerobic gut flora, was studied in normal volunteers from southern India and the United States. Digoxin was metabolised to DRP by 28 (13.7%) of 204 healthy south Indians in contrast to 67 (36.0%) of 186 New Yorkers (p less than 1 X 10(-6)). Only 1.0% of Indians compared with 14.0% of Americans excreted large amounts of metabolites (greater than 40% DRP) in the urine (p less than 1 X 10(-5)). Of 104 urban Indians, 23 (22.1%) were metabolisers, in contrast with five of 100 rural villagers (p less than 0.001). Within the urban group, digoxin metabolism correlated with education, frequency of animal protein intake, and most significantly, personal income. Organisms capable of reducing digoxin in vitro were found with similar frequencies in stool cultures from Indians and Americans. In the cultures of some subjects, DRP production was inhibited at lower dilutions but expressed at higher dilutions. We conclude that variations in drug metabolism between population groups may result from differences in the metabolic activity of the anaerobic gut flora probably mediated by environmentally determined factors. PMID:2759492

  2. Acetylation of Werner syndrome protein (WRN): relationships with DNA damage, DNA replication and DNA metabolic activities

    PubMed Central

    Lozada, Enerlyn; Yi, Jingjie; Luo, Jianyuan; Orren, David K.

    2014-01-01

    Loss of WRN function causes Werner Syndrome, characterized by increased genomic instability, elevated cancer susceptibility and premature aging. Although WRN is subject to acetylation, phosphorylation and sumoylation, the impact of these modifications on WRN’s DNA metabolic function remains unclear. Here, we examined in further depth the relationship between WRN acetylation and its role in DNA metabolism, particularly in response to induced DNA damage. Our results demonstrate that endogenous WRN is acetylated somewhat under unperturbed conditions. However, levels of acetylated WRN significantly increase after treatment with certain DNA damaging agents or the replication inhibitor hydroxyurea. Use of DNA repair-deficient cells or repair pathway inhibitors further increase levels of acetylated WRN, indicating that induced DNA lesions and their persistence are at least partly responsible for increased acetylation. Notably, acetylation of WRN correlates with inhibition of DNA synthesis, suggesting that replication blockage might underlie this effect. Moreover, WRN acetylation modulates its affinity for and activity on certain DNA structures, in a manner that may enhance its relative specificity for physiological substrates. Our results also show that acetylation and deacetylation of endogenous WRN is a dynamic process, with sirtuins and other histone deacetylases contributing to WRN deacetylation. These findings advance our understanding of the dynamics of WRN acetylation under unperturbed conditions and following DNA damage induction, linking this modification not only to DNA damage persistence but also potentially to replication stalling caused by specific DNA lesions. Our results are consistent with proposed metabolic roles for WRN and genomic instability phenotypes associated with WRN deficiency. PMID:24965941

  3. Composition and Metabolic Activities of Bacterial Biofilms Colonizing Food Residues in the Human Gut

    PubMed Central

    Macfarlane, Sandra; Macfarlane, George T.

    2006-01-01

    Bacteria growing in the human large intestine live in intimate association with the host and play an important role in host digestive processes, gut physiology, and metabolism. Fecal bacteria have been investigated extensively, but few studies have been done on biofilms that form on digestive wastes in the large bowel. The aims of this investigation were to investigate the composition and metabolic activities of bacterial communities that colonize the surfaces of food residues in fecal material, with respect to their role in the fermentation of complex carbohydrates. Fresh stools were obtained from 15 healthy donors, and food residues were separated by filtration. Adherent bacteria were removed by surfactant treatment for microbiological analysis and fermentation studies. Scanning electron microscopy and fluorescent in situ hybridization in conjunction with confocal laser scanning microscopy (CLSM) were used to visualize intact biofilms. Results showed that bacterial populations strongly adhering to particulate matter were phenotypically similar in composition to unattached communities, with bacteroides and bifidobacteria predominating. Biofilms comprised a mixture of living and dead bacteria, and CLSM showed that bifidobacteria in the biofilms occurred as isolated dispersed cells and in microcolonies near the interface with the substratum. Fermentation experiments with a variety of complex carbohydrates demonstrated that biofilm populations were more efficient in digesting polysaccharides, while nonadhering communities fermented oligosaccharides most rapidly. Acetate was the principal fermentation product formed by biofilm bacteria, whereas higher levels of butyrate were produced by nonadherent populations, showing that the two communities were metabolically distinct. PMID:16957247

  4. Distribution of zooplankton biomass and potential metabolic activities across the northern Benguela upwelling system

    NASA Astrophysics Data System (ADS)

    Fernández-Urruzola, I.; Osma, N.; Packard, T. T.; Gómez, M.; Postel, L.

    2014-11-01

    The distribution of zooplankton biomass and potential metabolic rates, in terms of electron transport system (ETS) and glutamate dehydrogenase (GDH), were analyzed along a cross-shelf transect in waters off Namibia. The highly variable dynamics of upwelling filaments promoted short-term fluctuations in the zooplankton biomass and metabolism. Maximum values were characteristically found over the shelf-break, where zooplankton biomass as dry mass (DM) reached peaks of 64.5 mg m- 3 within the upper 200 m in late August. Two weeks later, the zooplankton-DM decreased by more than a third (19 mg DM m- 3). Zooplankton potential respiration and NH4+ excretion averaged 234 μmol O2 m- 3 d- 1 and 169 μmol NH4+ m- 3 d- 1 in the Namibian shelf, respectively. High protein-specific ETS activities even in the low-chlorophyll waters outside the filament suggested a shift into greater omnivory seaward. In this light, zooplankton elemental and isotopic compositions were used to investigate the pelagic food web interactions. They evidenced spatial changes in the carbon resource for zooplankton as well as changes in the form of nitrogen that fueled the biological production in aging advected waters. Overall, both aspects of zooplankton metabolism impacted the primary productivity at a level less than 10% under all the different oceanographic conditions.

  5. NF-Y activates genes of metabolic pathways altered in cancer cells

    PubMed Central

    Benatti, Paolo; Chiaramonte, Maria Luisa; Lorenzo, Mariangela; Hartley, John A.; Hochhauser, Daniel; Gnesutta, Nerina; Mantovani, Roberto; Imbriano, Carol; Dolfini, Diletta

    2016-01-01

    The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Specific cancer-driving nodes are generally under NF-Y control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production and other anabolic pathways commonly altered in cancer cells. PMID:26646448

  6. Ginsenoside Rf, a component of ginseng, regulates lipoprotein metabolism through peroxisome proliferator-activated receptor {alpha}

    SciTech Connect

    Lee, Hyunghee; Gonzalez, Frank J.; Yoon, Michung . E-mail: yoon60@mokwon.ac.kr

    2006-01-06

    We investigated whether ginseng regulates lipoprotein metabolism by altering peroxisome proliferator-activated receptor {alpha} (PPAR{alpha})-mediated pathways, using a PPAR{alpha}-null mouse model. Administration of ginseng extract, ginsenosides, and ginsenoside Rf (Rf) to wild-type mice not only significantly increased basal levels of hepatic apolipoprotein (apo) A-I and C-III mRNA compared with wild-type controls, but also substantially reversed the reductions in mRNA levels of apo A-I and C-III expected following treatment with the potent PPAR{alpha} ligand Wy14,643. In contrast, no effect was detected in the PPAR{alpha}-null mice. Testing of eight main ginsenosides on PPAR{alpha} reporter gene expression indicated that Rf was responsible for the effects of ginseng on lipoprotein metabolism. Furthermore, the inhibition of PPAR{alpha}-dependent transactivation by Rf seems to occur at the level of DNA binding. These results demonstrate that ginseng component Rf regulates apo A-I and C-III mRNA and the actions of Rf on lipoprotein metabolism are mediated via interactions with PPAR{alpha}.

  7. Metabolomics Reveals that Aryl Hydrocarbon Receptor Activation by Environmental Chemicals Induces Systemic Metabolic Dysfunction in Mice

    PubMed Central

    Zhang, Limin; Hatzakis, Emmanuel; Nichols, Robert G.; Hao, Ruixin; Correll, Jared; Smith, Philip B.; Chiaro, Christopher R.; Perdew, Gary H.; Patterson, Andrew D.

    2016-01-01

    Environmental exposure to dioxins and dioxin-like compounds poses a significant health risk for human health. Developing a better understanding of the mechanisms of toxicity through activation of the aryl hydrocarbon receptor (AHR) is likely to improve the reliability of risk assessment. In this study, the AHR-dependent metabolic response of mice exposed to 2,3,7,8-tetrachlorodibenzofuran (TCDF) were assessed using global 1H nuclear magnetic resonance (NMR)-based metabolomics and targeted metabolic profiling of extracts obtained from serum and liver. 1H NMR analyses revealed that TCDF exposure suppressed gluconeogenesis and glycogenolysis, stimulated lipogenesis, and triggered inflammatory gene expression in an Ahr-dependent manner. Targeted analyses using gas chromatography mass spectrometry showed TCDF treatment altered the ratio of unsaturated/saturated fatty acids. Consistent with this observation, an increase in hepatic expression of stearoyl coenzyme A desaturase 1 was also observed. In addition, TCDF exposure resulted in inhibition of de novo fatty acid biosynthesis manifested by down-regulation of acetyl-CoA, malonyl-CoA and palmitoyl-CoA metabolites and related mRNA levels. In contrast, no significant changes in the levels of glucose and lipid were observed in serum and liver obtained from Ahr-null mice following TCDF treatment, thus strongly supporting the important role of the AHR in mediating the metabolic effects seen following TCDF exposure. PMID:26023891

  8. Metabolic Profiles and Free Radical Scavenging Activity of Cordyceps bassiana Fruiting Bodies According to Developmental Stage

    PubMed Central

    Hyun, Sun-Hee; Lee, Seok-Young; Sung, Gi-Ho; Kim, Seong Hwan; Choi, Hyung-Kyoon

    2013-01-01

    The metabolic profiles of Cordyceps bassiana according to fruiting body developmental stage were investigated using gas chromatography-mass spectrometry. We were able to detect 62 metabolites, including 48 metabolites from 70% methanol extracts and 14 metabolites from 100% n-hexane extracts. These metabolites were classified as alcohols, amino acids, organic acids, phosphoric acids, purine nucleosides and bases, sugars, saturated fatty acids, unsaturated fatty acids, or fatty amides. Significant changes in metabolite levels were found according to developmental stage. Relative levels of amino acids, purine nucleosides, and sugars were higher in development stage 3 than in the other stages. Among the amino acids, valine, isoleucine, lysine, histidine, glutamine, and aspartic acid, which are associated with ABC transporters and aminoacyl-tRNA biosynthesis, also showed higher levels in stage 3 samples. The free radical scavenging activities, which were significantly higher in stage 3 than in the other stages, showed a positive correlation with purine nucleoside metabolites such as adenosine, guanosine, and inosine. These results not only show metabolic profiles, but also suggest the metabolic pathways associated with fruiting body development stages in cultivated C. bassiana. PMID:24058459

  9. The phytoestrogen genistein modulates lysosomal metabolism and transcription factor EB (TFEB) activation.

    PubMed

    Moskot, Marta; Montefusco, Sandro; Jakóbkiewicz-Banecka, Joanna; Mozolewski, Paweł; Węgrzyn, Alicja; Di Bernardo, Diego; Węgrzyn, Grzegorz; Medina, Diego L; Ballabio, Andrea; Gabig-Cimińska, Magdalena

    2014-06-13

    Genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) has been previously proposed as a potential drug for use in substrate reduction therapy for mucopolysaccharidoses, a group of inherited metabolic diseases caused by mutations leading to inefficient degradation of glycosaminoglycans (GAGs) in lysosomes. It was demonstrated that this isoflavone can cross the blood-brain barrier, making it an especially desirable potential drug for the treatment of neurological symptoms present in most lysosomal storage diseases. So far, no comprehensive genomic analyses have been performed to elucidate the molecular mechanisms underlying the effect elicited by genistein. Therefore, the aim of this work was to identify the genistein-modulated gene network regulating GAG biosynthesis and degradation, taking into consideration the entire lysosomal metabolism. Our analyses identified over 60 genes with known roles in lysosomal biogenesis and/or function whose expression was enhanced by genistein. Moreover, 19 genes whose products are involved in both GAG synthesis and degradation pathways were found to be remarkably differentially regulated by genistein treatment. We found a regulatory network linking genistein-mediated control of transcription factor EB (TFEB) gene expression, TFEB nuclear translocation, and activation of TFEB-dependent lysosome biogenesis to lysosomal metabolism. Our data indicate that the molecular mechanism of genistein action involves not only impairment of GAG synthesis but more importantly lysosomal enhancement via TFEB. These findings contribute to explaining the beneficial effects of genistein in lysosomal storage diseases as well as envisage new therapeutic approaches to treat these devastating diseases.

  10. Adenosine, Ketogenic Diet and Epilepsy: The Emerging Therapeutic Relationship Between Metabolism and Brain Activity

    PubMed Central

    Masino, S.A; Kawamura, M; Wasser, C.D.; Pomeroy, L.T; Ruskin, D.N

    2009-01-01

    For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a “retaliatory metabolite.” As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor–based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed. PMID:20190967

  11. New metabolic and pharmacokinetic characteristics of thiocolchicoside and its active metabolite in healthy humans.

    PubMed

    Trellu, M; Filali-Ansary, A; Françon, D; Adam, R; Lluel, P; Dubruc, C; Thénot, J P

    2004-08-01

    Thiocolchicoside (TCC) has been prescribed for several years as a muscle relaxant drug, but its pharmacokinetic (PK) profile and metabolism still remain largely unknown. Therefore, we re-investigated its metabolism and PK, and we assessed the muscle relaxant properties of its metabolites. After oral administration of 8 mg (a therapeutic dose) of 14C-labelled TCC to healthy volunteers, we found no detectable TCC in plasma, urine or faeces. On the other hand, the aglycone derivative obtained after de-glycosylation of TCC (M2) was observed and, in addition, we identified, as the major circulating metabolic entity, 3-O-glucuronidated aglycone (M1) obtained after glucuro-conjugation of M2. One hour after oral administration, M1 plus M2 accounted for more than 75% of the circulating total radioactivity. The pharmacological activity of these metabolites was assessed using a rat model, the muscle relaxant activity of M1 was similar to that of TCC whereas M2 was devoid of any activity. Subsequently, to investigate the PK profile of TCC in human PK studies, we developed and validated a specific bioanalytical method that combines liquid chromatography and ultraviolet detection to assay both active entities. After oral administration, TCC was not quantifiable with an lower limit of quantification set at 1 ng/mL, whereas its active metabolite M1 was detected. M1 appeared rapidly in plasma (tmax=1 h) and was eliminated with an apparent terminal half-life of 7.3 h. In contrast, after intramuscular administration both active entities (TCC and M1) were present; TCC was rapidly absorbed (tmax=0.4 h) and eliminated with an apparent terminal half-life of 1.5 h. M1 concentration peaked at 5 h and this metabolite was eliminated with an apparent terminal half-life of 8.6 h. As TCC and M1 present an equipotent pharmacological activity, the relative oral pharmacological bioavailability of TCC vs. intramuscular administration was calculated and represented 25%. Therefore, to correctly

  12. Effects of sex and site on amino acid metabolism enzyme gene expression and activity in rat white adipose tissue

    PubMed Central

    Arriarán, Sofía; Agnelli, Silvia; Remesar, Xavier; Fernández-López, José Antonio

    2015-01-01

    Background and Objectives. White adipose tissue (WAT) shows marked sex- and diet-dependent differences. However, our metabolic knowledge of WAT, especially on amino acid metabolism, is considerably limited. In the present study, we compared the influence of sex on the amino acid metabolism profile of the four main WAT sites, focused on the paths related to ammonium handling and the urea cycle, as a way to estimate the extent of WAT implication on body amino-nitrogen metabolism. Experimental Design. Adult female and male rats were maintained, undisturbed, under standard conditions for one month. After killing them under isoflurane anesthesia. WAT sites were dissected and weighed. Subcutaneous, perigonadal, retroperitoneal and mesenteric WAT were analyzed for amino acid metabolism gene expression and enzyme activities. Results. There was a considerable stability of the urea cycle activities and expressions, irrespective of sex, and with only limited influence of site. Urea cycle was more resilient to change than other site-specialized metabolic pathways. The control of WAT urea cycle was probably related to the provision of arginine/citrulline, as deduced from the enzyme activity profiles. These data support a generalized role of WAT in overall amino-N handling. In contrast, sex markedly affected WAT ammonium-centered amino acid metabolism in a site-related way, with relatively higher emphasis in males’ subcutaneous WAT. Conclusions. We found that WAT has an active amino acid metabolism. Its gene expressions were lower than those of glucose-lipid interactions, but the differences were quantitatively less important than usually reported. The effects of sex on urea cycle enzymes expression and activity were limited, in contrast with the wider variations observed in other metabolic pathways. The results agree with a centralized control of urea cycle operation affecting the adipose organ as a whole. PMID:26587356

  13. Metabolic Potential and Activity in Fluids of the Coast Range Ophiolite Microbial Observatory, California, USA

    NASA Technical Reports Server (NTRS)

    Hoehler, T.; Som, S.; Schrenk, M.; McCollom, T.; Cardace, D.

    2016-01-01

    Metabolic potential and activity associated with hydrogen and carbon monoxide were characterized in fluids sampled from the the Coast Range Ophiolite Microbial Observatory (CROMO). CROMO consists of two clusters of science-dedicated wells drilled to varying depths up to 35m in the actively serpentinizing, Jurassic-age Coast Range Ophiolite of Northern California, along with a suite of pre-existing monitoring wells at the same site. Consistent with the fluid chemistry observed in other serpentinizing systems, CROMO fluids are highly alkaline, with pH up to 12.5, high in methane, with concentrations up 1600 micromolar, and low in dissolved inorganic carbon (DIC), with concentrations of 10's to 100's of micromolar. CROMO is conspicuous for fluid H2 concentrations that are consistently sub-micromolar, orders of magnitude lower than is typical of other systems. However, higher H2 concentrations (10's -100's of micromolar) at an earlier stage of fluid chemical evolution are predicted by, or consistent with: thermodynamic models for fluid chemistry based on parent rock composition equivalent to local peridotite and with water:rock ratio constrained by observed pH; the presence of magnetite at several wt% in CROMO drill cores; and concentrations of formate and carbon monoxide that would require elevated H2 if formed in equilibrium with H2 and DIC. Calculated Gibbs energy changes for reaction of H2 and CO in each of several metabolisms, across the range of fluid composition encompassed by the CROMO wells, range from bioenergetically feasible (capable of driving ATP synthesis) to thermodynamically unfavorable. Active consumption relative to killed controls was observed for both CO and H2 during incubation of fluids from the pre-existing monitoring wells; in incubations of freshly cored solids, consumption was only observed in one sample set (corresponding to the lowest pH) out of three. The specific metabolisms by which H2 and CO are consumed remain to be determined.

  14. Modeling and Classification of Kinetic Patterns of Dynamic Metabolic Biomarkers in Physical Activity.

    PubMed

    Breit, Marc; Netzer, Michael; Weinberger, Klaus M; Baumgartner, Christian

    2015-08-01

    The objectives of this work were the classification of dynamic metabolic biomarker candidates and the modeling and characterization of kinetic regulatory mechanisms in human metabolism with response to external perturbations by physical activity. Longitudinal metabolic concentration data of 47 individuals from 4 different groups were examined, obtained from a cycle ergometry cohort study. In total, 110 metabolites (within the classes of acylcarnitines, amino acids, and sugars) were measured through a targeted metabolomics approach, combining tandem mass spectrometry (MS/MS) with the concept of stable isotope dilution (SID) for metabolite quantitation. Biomarker candidates were selected by combined analysis of maximum fold changes (MFCs) in concentrations and P-values resulting from statistical hypothesis testing. Characteristic kinetic signatures were identified through a mathematical modeling approach utilizing polynomial fitting. Modeled kinetic signatures were analyzed for groups with similar behavior by applying hierarchical cluster analysis. Kinetic shape templates were characterized, defining different forms of basic kinetic response patterns, such as sustained, early, late, and other forms, that can be used for metabolite classification. Acetylcarnitine (C2), showing a late response pattern and having the highest values in MFC and statistical significance, was classified as late marker and ranked as strong predictor (MFC = 1.97, P < 0.001). In the class of amino acids, highest values were shown for alanine (MFC = 1.42, P < 0.001), classified as late marker and strong predictor. Glucose yields a delayed response pattern, similar to a hockey stick function, being classified as delayed marker and ranked as moderate predictor (MFC = 1.32, P < 0.001). These findings coincide with existing knowledge on central metabolic pathways affected in exercise physiology, such as β-oxidation of fatty acids, glycolysis, and glycogenolysis. The presented modeling approach

  15. Deciphering the role of aspartate and prephenate aminotransferase activities in plastid nitrogen metabolism.

    PubMed

    de la Torre, Fernando; El-Azaz, Jorge; Avila, Concepción; Cánovas, Francisco M

    2014-01-01

    Chloroplasts and plastids of nonphotosynthetic plant cells contain two aspartate (Asp) aminotransferases: a eukaryotic type (Asp5) and a prokaryotic-type bifunctional enzyme displaying Asp and prephenate aminotransferase activities (PAT). We have identified the entire Asp aminotransferase gene family in Nicotiana benthamiana and isolated and cloned the genes encoding the isoenzymes with plastidic localization: NbAsp5 and NbPAT. Using a virus-induced gene silencing approach, we obtained N. benthamiana plants silenced for NbAsp5 and/or NbPAT. Phenotypic and metabolic analyses were conducted in silenced plants to investigate the specific roles of these enzymes in the biosynthesis of essential amino acids within the plastid. The NbAsp5 silenced plants had no changes in phenotype, exhibiting similar levels of free Asp and glutamate as control plants, but contained diminished levels of asparagine and much higher levels of lysine. In contrast, the suppression of NbPAT led to a severe reduction in growth and strong chlorosis symptoms. NbPAT silenced plants exhibited extremely reduced levels of asparagine and were greatly affected in their phenylalanine metabolism and lignin deposition. Furthermore, NbPAT suppression triggered a transcriptional reprogramming in plastid nitrogen metabolism. Taken together, our results indicate that NbPAT has an overlapping role with NbAsp5 in the biosynthesis of Asp and a key role in the production of phenylalanine for the biosynthesis of phenylpropanoids. The analysis of NbAsp5/NbPAT cosilenced plants highlights the central role of both plastidic aminotransferases in nitrogen metabolism; however, only NbPAT is essential for plant growth and development.

  16. Modeling and Classification of Kinetic Patterns of Dynamic Metabolic Biomarkers in Physical Activity

    PubMed Central

    Breit, Marc; Netzer, Michael

    2015-01-01

    The objectives of this work were the classification of dynamic metabolic biomarker candidates and the modeling and characterization of kinetic regulatory mechanisms in human metabolism with response to external perturbations by physical activity. Longitudinal metabolic concentration data of 47 individuals from 4 different groups were examined, obtained from a cycle ergometry cohort study. In total, 110 metabolites (within the classes of acylcarnitines, amino acids, and sugars) were measured through a targeted metabolomics approach, combining tandem mass spectrometry (MS/MS) with the concept of stable isotope dilution (SID) for metabolite quantitation. Biomarker candidates were selected by combined analysis of maximum fold changes (MFCs) in concentrations and P-values resulting from statistical hypothesis testing. Characteristic kinetic signatures were identified through a mathematical modeling approach utilizing polynomial fitting. Modeled kinetic signatures were analyzed for groups with similar behavior by applying hierarchical cluster analysis. Kinetic shape templates were characterized, defining different forms of basic kinetic response patterns, such as sustained, early, late, and other forms, that can be used for metabolite classification. Acetylcarnitine (C2), showing a late response pattern and having the highest values in MFC and statistical significance, was classified as late marker and ranked as strong predictor (MFC = 1.97, P < 0.001). In the class of amino acids, highest values were shown for alanine (MFC = 1.42, P < 0.001), classified as late marker and strong predictor. Glucose yields a delayed response pattern, similar to a hockey stick function, being classified as delayed marker and ranked as moderate predictor (MFC = 1.32, P < 0.001). These findings coincide with existing knowledge on central metabolic pathways affected in exercise physiology, such as β-oxidation of fatty acids, glycolysis, and glycogenolysis. The presented modeling approach

  17. Acute effects of active gaming on ad libitum energy intake and appetite sensations of 8-11-year-old boys.

    PubMed

    Allsop, Susan; Dodd-Reynolds, Caroline J; Green, Benjamin P; Debuse, Dorothée; Rumbold, Penny L S

    2015-12-28

    The present study examined the acute effects of active gaming on energy intake (EI) and appetite responses in 8-11-year-old boys in a school-based setting. Using a randomised cross-over design, twenty-one boys completed four individual 90-min gaming bouts, each separated by 1 week. The gaming bouts were (1) seated gaming, no food or drink; (2) active gaming, no food or drink; (3) seated gaming with food and drink offered ad libitum; and (4) active gaming with food and drink offered ad libitum. In the two gaming bouts during which foods and drinks were offered, EI was measured. Appetite sensations - hunger, prospective food consumption and fullness - were recorded using visual analogue scales during all gaming bouts at 30-min intervals and at two 15-min intervals post gaming. In the two bouts with food and drink, no significant differences were found in acute EI (MJ) (P=0·238). Significant differences were detected in appetite sensations for hunger, prospective food consumption and fullness between the four gaming bouts at various time points. The relative EI calculated for the two gaming bouts with food and drink (active gaming 1·42 (sem 0·28) MJ; seated gaming 2·12 (sem 0·25) MJ) was not statistically different. Acute EI in response to active gaming was no different from seated gaming, and appetite sensations were influenced by whether food was made available during the 90-min gaming bouts.

  18. Quantitative studies on the in vitro metabolic activation of dimethylnitrosamine by rat liver postmitochondrial supernatant

    SciTech Connect

    Doolittle, D.J.; Goodman, J.I.

    1984-08-01

    The metabolic activation of dimethylnitrosamine (DMN) to mutagenic and/or cytotoxic intermediates in vitro has been characterized and the relationship between DMN demethylase and ethoxyresorufin-O-deethylase (EROD) or ethylmorphine-N-demethylase (EMND) has been evaluated. A mammalian assay system which uses the postmitochondrial supernatant (S-15 fraction) prepared from a rat liver homogenate as an enzyme source and V79 Chinese hamster cells as targets for chemically induced damage was used. The enzyme pattern of the S-15 fraction was altered by pretreatment of experimental animals in vivo and/or by the use of enzyme inhibitors in vitro. The results of these studies indicate that the concentration of S-15 fraction in the reaction mixture can markedly influence the degree of DMN-induced cytotoxicity when it is metabolized in vitro and that the degree of DMN-induced cytotoxicity and mutagenicity are linearly related. The degree of cytotoxicity and mutagenicity induced in V79 cells by DMN does not correlate with EROD activity (a measure of 3-methylcholanthrene-inducible mixed-function oxidases) nor with EMND activity (a measure of phenobarbital-inducible mixed function oxidases) in the S-15 fraction. 28 references, 4 figures.

  19. Aldehyde dehydrogenase activity in Lactococcus chungangensis: Application in cream cheese to reduce aldehyde in alcohol metabolism.

    PubMed

    Konkit, Maytiya; Choi, Woo Jin; Kim, Wonyong

    2016-03-01

    Previous studies have shown that the metabolic capability of colonic microflora may be at least as high as that of the liver or higher than that of the whole human body. Aldehyde dehydrogenase (ALDH) is an enzyme produced by these bacteria that can metabolize acetaldehyde, produce from ethanol to acetate. Lactococcus species, which is commonly used as a starter in dairy products, was recently found to possess the ALDH gene, and the activity of this enzyme was determined. In this study, the ALDH activity of Lactococcus chungangensis CAU 28(T) and 11 other type strains in the genus Lactococcus was studied. Only 5 species, 3 of dairy origin (Lactococcus lactis ssp. lactis KCTC 3769(T), Lactococcus lactis ssp. cremoris KCCM 40699(T), and Lactococcus raffinolactis DSM 20443(T)) and 2 of nondairy origin (Lactococcus fujiensis NJ317(T) and L. chungangensis CAU 28(T)), showed ALDH activity and possessed a gene encoding ALDH. All of these strains were capable of making cream cheese. Among the strains, L. chungangensis produced cream cheese that contained the highest level of ALDH and was found to reduce the level of acetaldehyde in the serum of mice. These results predict a promising role for L. chungangensis CAU28(T) to be used in cheese that can be developed as functional food.

  20. Metabolic stress–induced activation of FoxO1 triggers diabetic cardiomyopathy in mice

    PubMed Central

    Battiprolu, Pavan K.; Hojayev, Berdymammet; Jiang, Nan; Wang, Zhao V.; Luo, Xiang; Iglewski, Myriam; Shelton, John M.; Gerard, Robert D.; Rothermel, Beverly A.; Gillette, Thomas G.; Lavandero, Sergio; Hill, Joseph A.

    2012-01-01

    The leading cause of death in diabetic patients is cardiovascular disease; diabetic cardiomyopathy is typified by alterations in cardiac morphology and function, independent of hypertension or coronary disease. However, the molecular mechanism that links diabetes to cardiomyopathy is incompletely understood. Insulin resistance is a hallmark feature of diabetes, and the FoxO family of transcription factors, which regulate cell size, viability, and metabolism, are established targets of insulin and growth factor signaling. Here, we set out to evaluate a possible role of FoxO proteins in diabetic cardiomyopathy. We found that FoxO proteins were persistently activated in cardiac tissue in mice with diabetes induced either genetically or by high-fat diet (HFD). FoxO activity was critically linked with development of cardiomyopathy: cardiomyocyte-specific deletion of FoxO1 rescued HFD-induced declines in cardiac function and preserved cardiomyocyte insulin responsiveness. FoxO1-depleted cells displayed a shift in their metabolic substrate usage, from free fatty acids to glucose, associated with decreased accumulation of lipids in the heart. Furthermore, we found that FoxO1-dependent downregulation of IRS1 resulted in blunted Akt signaling and insulin resistance. Together, these data suggest that activation of FoxO1 is an important mediator of diabetic cardiomyopathy and is a promising therapeutic target for the disease. PMID:22326951

  1. Kaempferol ameliorates symptoms of metabolic syndrome by regulating activities of liver X receptor-β.

    PubMed

    Hoang, Minh-Hien; Jia, Yaoyao; Mok, Boram; Jun, Hee-jin; Hwang, Kwang-Yeon; Lee, Sung-Joon

    2015-08-01

    Kaempferol is a dietary flavonol previously shown to regulate cellular lipid and glucose metabolism. However, its molecular mechanisms of action and target proteins have remained elusive, probably due to the involvement of multiple proteins. This study investigated the molecular targets of kaempferol. Ligand binding of kaempferol to liver X receptors (LXRs) was quantified by time-resolved fluorescence resonance energy transfer and surface plasmon resonance analyses. Kaempferol directly binds to and induces the transactivation of LXRs, with stronger specificity for the β-subtype (EC50 = 0.33 μM). The oral administration of kaempferol in apolipoprotein-E-deficient mice (150 mg/day/kg body weight) significantly reduced plasma glucose and increased high-density lipoprotein cholesterol levels and insulin sensitivity compared with the vehicle-fed control. Kaempferol also reduced plasma triglyceride concentrations and did not cause liver steatosis, a common side effect of potent LXR activation. In immunoblotting analysis, kaempferol reduced the nuclear accumulation of sterol regulatory element-binding protein-1 (SREBP-1). Our results show that the suppression of SREBP-1 activity and the selectivity for LXR-β over LXR-α by kaempferol contribute to the reductions of plasma and hepatic triglyceride concentrations in mice fed kaempferol. They also suggest that kaempferol activates LXR-β and suppresses SREBP-1 to enhance symptoms in metabolic syndrome.

  2. Functional coupling of simultaneous electrical and metabolic activity in the human brain.

    PubMed

    Oakes, Terrence R; Pizzagalli, Diego A; Hendrick, Andrew M; Horras, Katherine A; Larson, Christine L; Abercrombie, Heather C; Schaefer, Stacey M; Koger, John V; Davidson, Richard J

    2004-04-01

    The relationships between brain electrical and metabolic activity are being uncovered currently in animal models using invasive methods; however, in the human brain this relationship remains not well understood. In particular, the relationship between noninvasive measurements of electrical activity and metabolism remains largely undefined. To understand better these relations, cerebral activity was measured simultaneously with electroencephalography (EEG) and positron emission tomography using [(18)f]-fluoro-2-deoxy-D-glucose (PET-FDG) in 12 normal human subjects during rest. Intracerebral distributions of current density were estimated, yielding tomographic maps for seven standard EEG frequency bands. The PET and EEG data were registered to the same space and voxel dimensions, and correlational maps were created on a voxel-by-voxel basis across all subjects. For each band, significant positive and negative correlations were found that are generally consistent with extant understanding of EEG band power function. With increasing EEG frequency, there was an increase in the number of positively correlated voxels, whereas the lower alpha band (8.5-10.0 Hz) was associated with the highest number of negative correlations. This work presents a method for comparing EEG signals with other more traditionally tomographic functional imaging data on a 3-D basis. This method will be useful in the future when it is applied to functional imaging methods with faster time resolution, such as short half-life PET blood flow tracers and functional magnetic resonance imaging.

  3. US space flight experience. Physical exertion and metabolic demand of extravehicular activity: Past, present, and future

    NASA Technical Reports Server (NTRS)

    Moore, Thomas P.

    1989-01-01

    A review of physical exertion and metabolic demands of extravehicular activity (EVA) on U.S. astronauts is given. Information is given on EVA during Gemini, Apollo and Skylab missions. It is noted that nominal EVA's should not be overstressful from a cardiovascular standpoint; that manual-intensive EVA's such as are planned for the construction phase of the Space Station can and will be demanding from a muscular standpoint, primarily for the upper extremities; that off-nominal unplanned EVA's can be physically demanding both from an endurance and from a muscular standpoint; and that crewmembers should be physically prepared and capable of performing these EVA's at any time during the mission.

  4. [Metabolically active volumes automatic delineation methodologies in PET imaging: review and perspectives].

    PubMed

    Hatt, M; Boussion, N; Cheze-Le Rest, C; Visvikis, D; Pradier, O

    2012-02-01

    PET imaging is now considered a gold standard tool in clinical oncology, especially for diagnosis purposes. More recent applications such as therapy follow-up or tumor targeting in radiotherapy require a fast, accurate and robust metabolically active tumor volumes delineation on emission images, which cannot be obtained through manual contouring. This clinical need has sprung a large number of methodological developments regarding automatic methods to define tumor volumes on PET images. This paper reviews most of the methodologies that have been recently proposed and discusses their framework and methodological and/or clinical validation. Perspectives regarding the future work to be done are also suggested.

  5. XPC silencing in normal human keratinocytes triggers metabolic alterations through NOX-1 activation-mediated reactive oxygen species.

    PubMed

    Rezvani, Hamid Reza; Rossignol, Rodrigue; Ali, Nsrein; Benard, Giovanni; Tang, Xiuwei; Yang, Hee Seung; Jouary, Thomas; de Verneuil, Hubert; Taïeb, Alain; Kim, Arianna L; Mazurier, Frédéric

    2011-06-01

    Cancer cells utilize complex mechanisms to remodel their bioenergetic properties. We exploited the intrinsic genomic stability of xeroderma pigmentosum C (XPC) to understand the inter-relationships between genomic instability, reactive oxygen species (ROS) generation, and metabolic alterations during neoplastic transformation. We showed that knockdown of XPC (XPC(KD)) in normal human keratinocytes results in metabolism remodeling through NADPH oxidase-1 (NOX-1) activation, which in turn leads to increased ROS levels. While enforcing antioxidant defenses by overexpressing catalase, CuZnSOD, or MnSOD could not block the metabolism remodeling, impaired NOX-1 activation abrogates both alteration in ROS levels and modifications of energy metabolism. As NOX-1 activation is observed in human squamous cell carcinomas (SCCs), the blockade of NOX-1 could be a target for the prevention and the treatment of skin cancers.

  6. XPC silencing in normal human keratinocytes triggers metabolic alterations through NOX-1 activation-mediated reactive oxygen species

    PubMed Central

    Rezvani, Hamid Reza; Rossignol, Rodrigue; Ali, Nsrein; Benard, Giovanni; Tang, Xiuwei; Yang, Hee Seung; Jouary, Thomas; de Verneuil, Hubert; Taïeb, Alain; Kim, Arianna L.; Mazurier, Frédéric

    2011-01-01

    Summary Cancer cells utilize complex mechanisms to remodel their bioenergetic properties. We exploited the intrinsic genomic stability of xeroderma pigmentosum C (XPC) to understand the interrelationships between genomic instability, reactive oxygen species (ROS) generation, and metabolic alterations during neoplastic transformation. We showed that knockdown of XPC (XPCKD) in normal human keratinocytes results in metabolism remodeling through NADPH oxidase-1 (NOX-1) activation, which in turn leads to increased ROS levels. While enforcing antioxidant defenses by overexpressing catalase, CuZnSOD, or MnSOD could not block the metabolism remodeling, impaired NOX-1 activation abrogates both alteration in ROS levels and modifications of energy metabolism. As NOX-1 activation is observed in human squamous cell carcinomas (SCCs), the blockade of NOX-1 could be a target for the prevention and the treatment of skin cancers. PMID:21167810

  7. Student Perceptions of Value Added in an Active Learning Experience: Producing, Reviewing and Evaluating a Sales Team Video Presentation

    ERIC Educational Resources Information Center

    Corbett, James J.; Kezim, Boualem; Stewart, James

    2010-01-01

    This study investigates the effectiveness of a video team-based activity as a learning experience in a sales management course. Students perceived this learning <